Abstract
Allergenicity depends on several factors determined by the very physicochemical nature of the molecules themselves, i.e., their capacity to penetrate the horny layer, lipophilicity, and chemical reactivity. The sensitizing property of the majority of contact allergens could be predicted from these characteristics (Patlewicz GY, Basketter DA, Pease CK, Wilson K, Wright ZM, Roberts DW, Bernard G, Arnau EG, Lepoittevin JP (2004) Further evaluation of quantitative structure–activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens. Contact Dermatitis 50:91–97; Gerberick F, Aleksic M, Basketter D, Casati S, Karlberg AT, Kern P, Kimber I, Lepoittevin JP, Natsch A, Ovigne JM, Rovida C, Sakaguchi H, Schultz T (2008) Chemical reactivity measurement and the predicitve identification of skin sensitisers. The report and recommendations of ECVAM Workshop 64. Altern Lab Anim 36(2):215–242). Two other factors, however, further contribute to the allergenicity of chemicals, namely, their pro-inflammatory activity and capacity to induce maturation of LC. These issues will be dealt with in more detail in the following sections.
Along with their migration and settling within the draining lymph nodes, haptenized LC further mature, as characterized by their increased expression of costimulatory and antigen-presentation molecules (Cumberbatch M, Dearman RJ, Kimber I (1997) Interleukin 1-beta and the stimulation of Langerhans cell migration – comparisons with tumour necrosis factor alpha. Arch Dermatol Res 289:277–284; Heufler C, Koch F, Schuler G (1988) Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med 167:700–705). In addition, they adopt a strongly veiled, interdigitating appearance, thus maximizing the chances of productive encounters with naive T lymphocytes and recognition of altered self (Steinman RM, Hoffman L, Pope M (1995) Maturation and migration of cutaneous dendritic cells. J Invest Dermatol 105:2S–7S; Furue M, Chang CH, Tamaki K (1996) Interleukin-1 but not tumor necrosis factor a synergistically upregulates the granulocyte-macrophage colony-stimulating factor-induced B7–1 expression of murine Langerhans cells. Br J Dermatol 135:194–198; Schuler G, Steinman RM (1985) Murine epidermal Langerhans cells mature into potent immune-stimulatory dendritic cells in vitro. J Exp Med 161:526–546).
The intricate structure of lymph node paracortical areas, the differential expression of chemokines and their receptors, the characteristic membrane ruffling of IDC, and the predominant circulation of naïve T lymphocytes through these lymph node areas provide optimal conditions for T-cell-receptor binding, i.e., the first signal for induction of T-cell activation (Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252). Intimate DC–T-cell contacts are further strengthened by secondary signals, provided by sets of cellular adhesion molecules, and growth-promoting cytokines (reviewed in Hommel M (2004) On the dynamics of T-cell activation in lymph nodes. Immunol Cell Biol 82:62–66; Cella M, Sallusto F, Lanzavecchia A (1997) Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 9:10–16).
In healthy individuals, primary skin contacts with contact allergens lead to differentiation and expansion of allergen-specific effector T cells displaying Th1, Th2, and/or Th17 cytokine profiles. The same allergens, if encountered along mucosal surfaces, favor the development of allergen-specific Th2 and Th17 effector cells, and/or Th3 and Tr1 allergen-specific regulatory T cells. Whereas the first two subsets may assist or replace Th1 cells in pro-inflammatory effector functions, the latter two subsets are mainly known for downregulating immune responsiveness. For most, if not all allergens, along with prolonged allergenic contacts, the role of Th2 cells as effector cells gradually increases given reduced longevity of Th1 responses.
The respective contributions of similar subsets of allergen-specific CD8+ T cells are still unknown, but distinct effector roles of allergen-specific Tc1 and Tc2 have been postulated.
Priming via the skin results in CLA positive T cells, which upon inflammatory stimuli preferentially enter the skin; on the other hand, gut homing T cells have been primed and generated along mucosal surfaces. Upon priming, T cells loose much of their capacity to recirculate via the lymph nodes, but gain the capacity to enter the tissues. In particular recently activated T cells will enter skin inflammatory sites. ACD reactions are primarily infiltrated by CD4 and/or CD8 pro-inflammatory cells, later reactions may be dominated by Th2 cells and regulatory T cells. Skin infiltation by T cells is fine-tuned by sets of adhesion molecules and chemokine receptors, whose expression is not rigid, but can be modulated by micro-environmental factors.
After antigenic activation the progeny of primed T cells is released via the efferent lymphatics into the bloodstream. Circulating allergen-specific cells can be challenged in vitro to provide diagnostic parameters for contact hypersensitivity. At least for water-soluble allergens, like metal salts, the degree of allergen-specific proliferation and cytokine production, in particular type-2 cytokines, correlate with clinical allergy. For routine application of a broad spectrum of allergens, culture conditions still need to be improved. For mechanistic in vitro studies in ACD, however, with selected sets of relatively nontoxic allergens, peripheral blood provides an excellent source of lymphocytes and antigen-presenting cells.
ACD reactions can be mediated by classical effector cells, i.e., allergen-specific CD4+ type-1 T cells which, upon triggering by allergen-presenting cells, produce IFN-γ to activate nonspecific inflammatory cells like macrophages. However, CD8+ T cells, and other cytokines, including IL-4, IL-17, and IL-22 can also play major roles in ACD. The conspicuous difference with DTH reactions induced by intradermal administration of protein antigens, i.e., the epidermal infiltrate, can largely be attributed to hapten-induced chemokine release by keratinocytes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abe M, Kondo T, Xu H, Fairchild RL (1996) Interferon-gamma inducible protein (IP-10) expression is mediated by CD8+ T cells and is regulated by CD4+ T cells during the elicitation of contact hypersensitivity. J Invest Dermatol 107:360–366
Abe N, Katamura K, Shintaku N, Fukui T, Kiyomasu T, Lio J, Ueno H, Tai G, Mayumi M, Furusho K (1997) Prostaglandin E2 and IL-4 provide naïve CD4+ T cells with distinct inhibitory signals for the priming of IFN-gamma production. Cell Immunol 181:86–92
Acuto O, Michel F (2003) CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nat Rev Immunol 3:939–951
Adema GJ, Hartgers F, Verstraten R, de Vries E, Marland G, Menon S, Foster J, Xu Y, Nooyen P, McClanahan T, Bacon KB, Figdor CG (1997) A dendritic-cell-derived C–C chemokine that preferentially attracts naïve T cells. Nature 387:713–717
Aiba S, Tagami H (1999) Dendritic cell activation induced by various stimuli, e.g. exposure to microorganisms, their products, cytokines, and simple chemicals as well as adhesion to extracellular matrix. J Dermatol Sci 20:1–13
Allan SE, Broady R, Gregori S, Himmel ME, Locke N, Roncarolo MG, Bacchetta R, Levings MK (2008) CD4+ T-regulatory cells: toward therapy for human diseases. Immunol Rev 223:391–421
Altin JG, Sloan EK (1997) The role of CD45 and CD45-associated molecules in T cell activation. Immunol Cell Biol 75:430–445
Asada H, Linton J, Katz SI (1997) Cytokine gene expression during the elicitation phase of contact sensitivity – regulation by endogenous IL-4. J Invest Dermatol 108:406–411
Asherson GL, Dieli F, Sireci G, Salerno A (1996) Role of IL-4 in delayed type hypersensitivity. Clin Exp Immunol 103:1–4
Austrup F, Vestweber D, Borges E, Lohning M, Brauer R, Herz U, Renz H, Hallmann R, Scheffold A, Radbruch A, Hamann A (1997) P- and E selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues. Nature 385:81–83
Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252
Bangert C, Friedl J, Stary G, Stingl G, Kopp T (2003) Immunopathologic features of allergic contact dermatitis in humans: participation of plasmacytoid dendritic cells in the pathogenesis of the disease? J Invest Dermatol 121:1409–1418
Basso AS, Cheroutre H, Mucida D (2009) More stories on Th17 cells. Cell Res 19(4):399–411
Benson JM, Whitacre CC (1997) The role of clonal deletion and anergy in oral tolerance. Res Immunol 148:533–541
Berg DJ, Leach MW, Kuhn R, Rajewsky K, Muller W, Davidson NJ, Rennick D (1995) Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses. J Exp Med 182:99–108
Bergstresser PR (1989) Sensitization and elicitation of inflammation in contact dermatitis. In: Norris DA (ed) Immune mechanisms in cutaneous disease. Dekker, New York, pp 219–246
Birbeck M (1961) An electron microscope study of basal melanocytes and high level clear cells (Langerhans cells) in vitiligo. J Invest Dermatol 37:51–56
Blauvelt A, Hwang ST, Udey MC (2003) Allergic and immunologic diseases of the skin. J Allergy Clin Immunol 111:S560–S570
Blömeke B, Brans R, Coenraads PJ, Dickel H, Bruckner T, Hein DW, Heesen M, Merk HF, Kawakubo Y (2009) Para-phenylenediamine and allergic sensitization: risk modification by N-acetyltransferase 1 and 2 genotypes. Br J Dermatol 161(5):1130–1135
Boerrigter GH, Scheper RJ (1984) Local administration of the cytostatic drug 4-hydroperoxy-cyclophosphamde (4-HPCY) facilitates cell mediated immune reactions. Clin Exp Immunol 58:161–166
Boerrigter GH, Scheper RJ (1987) Local and systemic desensitization induced by repeated epicutaneous hapten application. J Invest Dermatol 88:3–7
Boerrigter GH, de Groot J, Scheper RJ (1986) Intradermal administration of 4-hydoperoxy-cyclophosphamde during contact sensitization potentiates effector T cell responsiveness in draining lymph nodes. Immunopharmacology 1:13–20
Borges E, Tietz W, Steegmaier M, Moll T, Hallmann R, Hamann A, Vestweber D (1997) P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin. J Exp Med 185:573–578
Bos JD, Meinardi MMHM (2000) The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol 9:165–169
Braathen LR (1980) Studies on human epidermal Langerhans cells. III. Induction of T lymphocyte response to nickel sulphate in sensitized individuals. Br J Dermatol 103:517–526
Brand CU, Hunger RE, Yawalkar N, Gerber HA, Schaffner T, Braathen LR (1999) Characterization of human skin-derived CD1a-positive lymph cells. Arch Dermatol Res 291:65–72
Brasch J, Burgard J, Sterry W (1992) Common pathways in allergic and irritant contact dermatitis. J Invest Dermatol 98:166–170
Breathnach SM (1988) The Langerhans cell. Centenary review. Br J Dermatol 119:463–469
Bretscher PA, Ogunremi O, Menon JN (1997) Distinct immunological states in murine cutaneous leishmaniasis by immunizing with different amounts of antigen: the generation of beneficial, potentially harmful, harmful and potentially extremely harmful states. Behring Inst Mitt 98:153–159
Bridoux F, Badou A, Saoudi A, Bernard L, Druet E, Pasquier R, Druet P, Pelletier L (1997) Transforming growth factor beta (TGF-beta)-dependent inhibition of T helper cell 2 (Th2)-induced autoimmunity by self-major histocompatibility complex (MHC) class II-specific, regulatory CD4+ T cell lines. J Exp Med 185:1769–1775
Buchanan KL, Murphy JW (1997) Kinetics of cellular infiltration and cytokine production during the efferent phase of a delayed-type hypersensitivity reaction. Immunology 90:189–197
Budinger L, Hertl M (2000) Immunologic mechanisms in hypersensitivity reactions to metal ions: an overview. Allergy 55:108–115
Calder PC, Bevan SJ, Newsholme EA (1992) The inhibition of T-lymphocyte proliferation by fatty acids is via an eicosanoid-independent mechanism. Immunology 75:108–115
Cantrell D (1996) T cell receptor signal transduction pathways. Annu Rev Immunol 14:259–274
Carroll JM, Crompton T, Seery JP, Watt FM (1997) Transgenic mice expressing IFN-gamma in the epidermis have eczema, hair hypopigmentation, and hair loss. J Invest Dermatol 108:412–422
Caux C, Ait-Yahia S, Chemin K, de Bouteiller O, Dieu-Nosjean MC, Homey B, Massacrier C, Vanbervliet B, Zlotnik A, Vicari A (2000) Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Semin Immunopathol 22:345–369
Cavani A, Mei D, Guerra E, Corinti S, Giani M, Pirrotta L, Puddu P, Girolomoni G (1998) Patients with allergic contact dermatitis to nickel and nonallergic individuals display different nickel-specific T cell responses. Evidence for the presence of effector CD8+ and regulatory CD4+ T cells. J Invest Dermatol 111:621–628
Cavani A, Nasorri F, Ottaviani C, Sebastiani S, De Pita O, Girolomoni G (2003) Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J Immunol 171:5760–5768
Cella M, Sallusto F, Lanzavecchia A (1997) Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 9:10–16
Chase MW (1946) Inhibition of experimental drug allergy by prior feeding of the sensitizing agent. Proc Soc Exp Biol Med 61:257–259
Christensen OB, Beckstead JH, Daniels TE, Maibach HI (1985) Pathogenesis of orally induced flare-up reactions at old patch sites in nickel allergy. Acta Derm Venereol 65:298–304
Claessen AME, von Blomberg BME, de Groot J, Wolvers DAE, Kraal G, Scheper RJ (1996) Reversal of mucosal tolerance by subcutaneous administration of interleukin-12 at the site of attempted sensitization. Immunology 88:363–367
Constant SL, Bottomly K (1997) Induction of Th1 and Th2 CD4+ T cell responses: the alternate approaches. Annu Rev Immunol 15:297–322
Constant SL, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K (1995) Extent of T cell receptor ligation can determine the functional differentiation of naïve CD4+ T cells. J Exp Med 5:1591–1596
Coulter EM, Jenkinson C, Farrell J, Lavergne SN, Pease C, White A, Aleksic M, Basketter D, Williams DP, King C, Pirmohamed M, Park BK, Naisbitt DJ (2010) Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individuals. J Invest Dermatol 130:161–174
Crivellato E, Vacca A, Ribatti D (2004) Setting the stage: an anatomist’s view of the immune system. Trends Immunol 25:210–217
Croft M, So T, Duan W, Soroosh P (2009) The significance of OX40 and OX40L to T-cell biology and immune disease. Immunol Rev 229(1):173–191
Cumberbatch M, Dearman RJ, Kimber I (1997) Interleukin 1-beta and the stimulation of Langerhans cell migration – comparisons with tumour necrosis factor alpha. Arch Dermatol Res 289:277–284
Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A (2002) Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann N Y Acad Sci 966:131–142
Czernielewski SM, Demarchez M (1987) Further evidence for the self-reproducing capacity of Langerhans cells in human skin. J Invest Dermatol 88:17–20
Dabbagh K, Lewis DB (2003) Toll-like receptors and T-helper-1/T-helper-2 responses. Curr Opin Infect Dis 16:199–204
Davis SJ, van der Merwe PA (2003) TCR triggering: co-receptor-dependent or -independent? Trends Immunol 24:624–626
De Panfilis G (1998) CD8+ cytolytic T lymphocytes and the skin. Exp Dermatol 7:121–131
Demeure CE, Yang LP, Desjardins C, Raynauld P, Delespesse G (1997) Prostaglandin E-2 primes naïve T cells for the production of anti-inflammatory cytokines. Eur J Immunol 27:3526–3531
Dieli F, Ptak W, Sireci G, Romano GC, Potestio M, Salerno A, Asherson GL (1998) Cross-talk between V-beta-8(+) and gamma-delta(+) T lymphocytes in contact sensitivity. Immunology 93:469–477
Dieu M-C, Vanbervliet B, Vicari A, Bridon J-M, Oldham E, Ait-Yahia S, Brière F, Zlotnik A, Lebecque S, Caux C (1998) Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J Exp Med 188:373–386
Divkovic M, Pease CK, Gerberick GF, Basketter DA (2005) Hapten-protein binding: from theory to practical application in the in vitro prediction of skin sensitization. Contact Dermatitis 53(4):189–200
Dong C (2008) TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol 8(5):337–348
Dong C, Nurieva RI, Prasad DV (2003) Immune regulation by novel costimulatory molecules. Immunol Res 28:39–48
Dvorak HF, Mihm MC Jr, Dvorak AM (1976) Morphology of delayed-type hypersensitivity reactions in man. J Invest Dermatol 64:391–401
Edele F, Esser PR, Lass C, Laszczyk MN, Oswald E, Strüh CM, Rensing-Ehl A, Martin SF (2007) Innate and adaptive immune responses in allergic contact dermatitis and autoimmune skin diseases. Inflamm Allergy Drug Targets 6(4):236–244
Eliasson E, Kenna JG (1996) Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol Pharmacol 50:573–582
Enk AH, Katz SI (1992a) Early molecular events in the induction phase of contact sensitivity. Proc Natl Acad Sci USA 89:1398–1402
Enk AH, Katz SI (1992b) Identification and induction of keratinocyte-derived IL-10. J Immunol 149:92–95
Enk AH, Angeloni VL, Udey MC, Katz SI (1993) An essential role for Langerhans cell-derived IL-1b in the initiation of primary immune responses in skin. J Immunol 150:3698–3704
Epling GA, Wells JL, Yoon UC (1988) Photochemical transformations in salicylanilide photoallergy. Photochem Photobiol 47:167–171
Epstein WL (1987) The poison ivy picker of Pennypack Park: the continuing saga of poison ivy. J Invest Dermatol 88:7–9
Epstein SP, Baer RL, Thorbecke GJ, Belsito DV (1991) Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response. J Invest Dermatol 96:832–837
Faria AM, Weiner HL (2006) Oral tolerance and TGF-beta-producing cells. Inflamm Allergy Drug Targets 5(3):179–190
Ferber I, Schönrich G, Schenkel J, Mellor AL, Hämmerling GJ, Arnold B (1994) Levels of peripheral T cell tolerance induced by different doses of tolerogen. Science 263:674–676
Flier J, Boorsma DM, Bruynzeel DP, van Beek PJ, Stoof TJ, Scheper RJ, Willemze R, Tensen CP (1999) The CXCR3 activating chemokines IP-10, MIG and IP-9 are expressed in allergic but not in irritant patch test reactions. J Invest Dermatol 113:574–578
Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ, Glovsky MM, Eddy SM, Ward PA (1994) C5a-induced expression of P-selectin in endothelial cells. J Clin Invest 94:1147–1155
Fowler E, Weiner HL (1997) Oral tolerance: elucidation of mechanisms and application to treatment of autoimmune diseases. Biopolymers 43:323–335
Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS (1997) Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature 389:978–981
Furue M, Chang CH, Tamaki K (1996) Interleukin-1 but not tumor necrosis factor a synergistically upregulates the granulocyte-macrophage colony-stimulating factor-induced B7–1 expression of murine Langerhans cells. Br J Dermatol 135:194–198
Fyhrquist-Vanni N, Alenius H, Lauerma A (2007) Contact dermatitis. Dermatol Clin 25(4):613–623
Gajewski TF, Fitch FW (1988) Antiproliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol 140:4245–4252
Gascoigne NR, Zal T (2004) Molecular interactions at the T cell-antigen-presenting cell interface. Curr Opin Immunol 16:114–119
Gaspari AA, Jenkins MK, Katz SI (1988) Class II MCH-bearing keratinocytes induce antigen-specific unresponsiveness in hapten-specific TH1 clones. J Immunol 141:2216–2220
Geenen V, Brilot F (2003) Role of the thymus in the development of tolerance and autoimmunity towards the neuroendocrine system. Ann N Y Acad Sci 992:186–195
Gell PDH, Coombs RRA, Lachman R (1975) Clinical aspects of immunology, 3rd edn. Blackwell, London
Gerberick F, Aleksic M, Basketter D, Casati S, Karlberg AT, Kern P, Kimber I, Lepoittevin JP, Natsch A, Ovigne JM, Rovida C, Sakaguchi H, Schultz T (2008) Chemical reactivity measurement and the predicitve identification of skin sensitisers. The report and recommendations of ECVAM Workshop 64. Altern Lab Anim 36(2):215–242
Girolomoni G, Gisondi P, Ottaviani C, Cavani A (2004) Immunoregulation of allergic contact dermatitis. J Dermatol 31:264–270
Goebeler M, Meinardus-Hager G, Roth J, Goerdt S, Sorg C (1993) Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells. J Invest Dermatol 100:759–765
Goebeler M, Roth J, Brocker EB, Sorg C, Schulze-Osthoff K (1995) Activation of nuclear factor-kappa B and gene expression in human endothelial cells by the common haptens nickel and cobalt. J Immunol 155:2459–2467
Grewe M, Bruijnzeel-Koomen CA, Schöpf E, Thepen T, Langeveld-Wildschut AG, Ruzicka T, Krutmann J (1998) A role for Th1 and Th2 cells in the immunopathogenesis of atopic dermatitis. Immunol Today 19(8):359–361
Griem P, Wulferink M, Sachs B, Gonzales JB, Gleichmann E (1998) Allergic and autoimmune reactions to xenobiotics: how do they arise? Immunol Today 19:133–141
Groux H, Sornasse T, Cottrez F, de Vries JE, Coffman RL, Roncarolo MG, Yssel H (1997) Induction of human T helper cell type-1 differentiation results in loss of IFN-g receptor b-chain expression. J Immunol 158:5627–5631
Groves RW, Allen MH, Ross EL, Barker JN, MacDonald DM (1995) Tumor necrosis factor alpha is pro-inflammatory in normal human skin and modulates cutaneous adhesion molecule expression. Br J Dermatol 132:345–352
Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT (1998) A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naïve T lymphocytes. Proc Natl Acad Sci USA 95:258–263
Hafler DA, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Fukaura H (1997) Oral administration of myelin induces antigen-specific TGF-beta 1 secreting T cells in patients with multiple sclerosis. Ann N Y Acad Sci 835:120–131
Haig DM, Hopkins J, Miller HRP (1999) Local immune responses in afferent and efferent lymph. Immunology 96:155–163
Herzog WR, Meade R, Pettinicchi A, Ptak W, Askenase PW (1989) Nude mice produce a T cell-derived antigen-binding factor that mediates the early component of delayed-type hypersensitivity. J Immunol 142:1803–1812
Heufler C, Koch F, Schuler G (1988) Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med 167:700–705
Hill S, Edwards AJ, Kimber I, Knight SC (1990) Systemic migration of dendritic cells during contact sensitization. Immunology 71:277–281
Hindsen M, Christensen OB (1992) Delayed hypersensitivity reactions following allergic and irritant inflammation. Acta Derm Venereol 72:220–221
Hindsen M, Bruze M, Christensen OB (2001) Flare-up reactions after oral challenge with nickel in relation to challenge dose and intensity and time of previous patch test reactions. J Am Acad Dermatol 44:616–623
Hoath SB, Leahy DG (2003) The organization of human epidermis: functional epidermal units and phi proportionality. J Invest Dermatol 121:1440–1446
Hoefakker S, Caubo M, van Herve EHM, Roggeveen MJ, Boersma WJA, Van’t Joost Th, Notten WRF, Claassen E (1995) In vivo cytokine profiles in allergic and irritant contact dermatitis. Contact Dermatitis 33:258–266
Hommel M (2004) On the dynamics of T-cell activation in lymph nodes. Immunol Cell Biol 82:62–66
Honig SM, Fu S, Mao X, Yopp A, Gunn MD, Randolph GJ, Bromberg JS (2003) FTY720 stimulates multidrug transporter- and cysteinyl leukotriene-dependent T cell chemotaxis to lymph nodes. J Clin Invest 111:627–637
Houck G, Saeed S, Stevens GL, Morgan MB (2004) Eczema and the spongiotic dermatoses: a histologic and pathogenic update. Semin Cutan Med Surg 23:39–45
Hoyer KK, Dooms H, Barron L, Abbas AK (2008) Interleukin-2 in the development and control of inflammatory disease. Immunol Rev 226:19–28
Iliev ID, Mileti E, Matteoli G, Chieppa M, Rescigno M (2009) Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning. Mucosal Immunol 2(4):340–350
Inaba K, Schuler G, Witmer MD, Valinsky J, Atassi B, Steinman RM (1986) Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J Exp Med 164:605–613
Inaba K, Schuler G, Steinman RM (1993) GM-CSF – a granulocyte/macrophage/dendritic cell stimulating factor. In: Van Furth R (ed) Hemopoietic growth factors and mononuclear phagocytes. Karger, Basel, pp 187–196
Inerot A, Moller H (2000) Symptoms and signs reported during patch testing. Am J Contact Dermatol 11:49–52
Isaksson M, Bruze M (2003) Late patch-test reactions to budesonide need not be a sign of sensitization induced by the test procedure. Am J Contact Dermatol 14:154–156
Itano AA, Jenkins MK (2003) Antigen presentation to naive CD4 T cells in the lymph node. Nat Immunol 4:733–739
Iversen L, Johansen C (2008) Inflammasomes and inflammatory caspases in skin inflammation. Expert Rev Mol Diagn 8(6):697–705
Izcue A, Coombes JL, Powrie F (2009) Regulatory lymphocytes and intestinal inflammation. Annu Rev Immunol 27:313–338
Jakob T, Udey MC (1998) Regulation of E-cadherin mediated adhesion in Langerhans cell-like dendritic cells by inflammatory mediators that mobilize Langerhans cells in vivo. J Immunol 160:4067–4073
Jakob T, Ring J, Udey MC (2001) Multistep navigation of Langerhans/dendritic cells in and out of the skin. J Allergy Clin Immunol 108:688–696
Jensen CS, Menne T, Lisby S, Kristiansen J, Veien NK (2003) Experimental systemic contact dermatitis from nickel: a dose–response study. Contact Dermatitis 49:124–132
Kalinski P, Hilkens CMU, Snijders A, Snijdewint FGM, Kapsenberg ML (1997) IL-12 deficient dendritic cells, generated in the presence of prostaglandin E2, promote type-2 cytokine production in maturing human naïve T helper cells. J Immunol 159:28–35
Kalinski P, Schuitemaker JH, Hilkens CM, Kapsenberg ML (1998) Prostaglandin E2 induces the final maturation of IL-12 deficient CD1a + CD83+ dendritic cells. J Immunol 161:2804–2809
Kalish RS, Wood JA, LaPorte A (1994) Processing of urushiol (poison ivy) hapten by both endogenous and exogenous pathways for presentation to T cells in vitro. J Clin Invest 93:2039–2047
Kanerva L, Hyry H, Jolanki R, Hytonen M, Estlander T (1997) Delayed and immediate allergy caused by methylhexahydrophthalic anhydride. Contact Dermatitis 36:34–38
Kang KF, Kubin M, Cooper KD, Lessin SR, Trinchieri G, Rook AH (1996) IL-12 synthesis by human Langerhans cells. J Immunol 156:1402–1407
Karlberg AT, Bergström MA, Börje A, Luthman K, Nilsson JL (2008) Allergic contact dermatitis–formation, structural requirements, and reactivity of skin sensitizers. Chem Res Toxicol 21(1):53–69
Kidd P (2003) Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8:223–246
Kim CH, Broxmeyer HE (1999) Chemokines: signal lamps for trafficking of T and B cells for development and effector function. J Leukoc Biol 65:6–15
Kimber I, Cumberbatch M (1992) Dendritic cells and cutaneous immune responses to chemical allergens. Toxicol Appl Pharmacol 117:137–146
Kimber I, Dearman RJ (2002) Allergic contact dermatitis: the cellular effectors. Contact Dermatitis 46:1–5
Kimber I, Dearman RJ (2003) What makes a chemical an allergen? Ann Allergy Asthma Immunol 90:28–31
Kimber I, Dearman RJ, Cumberbatch M, Huby RJ (1998) Langerhans cells and chemical allergy. Curr Opin Immunol 10:614–619
Kimber I, Basketter DA, Gerberick GF, Dearman RJ (2002) Allergic contact dermatitis. Int Immunopharmacol 2:201–211
Kitagaki H, Fujisawa S, Watanabe K, Hayakawa K, Shiohara T (1995) Immediate-type hypersensitivity response followed by late reaction is induced by repeated epicutaneous application of contact sensitizing agents in mice. J Invest Dermatol 105:749–755
Knop J, Stremmer R, Neumann C, Dc Maeyer D, Macher E (1982) Interferon inhibits the suppressor T cell response of delayed-type hypersensitivity. Nature 296:775–776
Kobayashi Y (1997) Langerhans cells produce type IV collagenase (MMP-9) following epicutaneous stimulation with haptens. Immunology 90:496–501
Kondo S, Sauder DN (1995) Epidermal cytokines in allergic contact dermatitis. J Am Acad Dermatol 33:786–800
Korn T, Bettelli E, Oukka M, Kuchroo VK (2009) IL-17 and Th17 cells (review). Annu Rev Immunol 27:485–517, PubMed PMID: 19132915
Kothny-Wilkes G, Kulms D, Poppelmann B, Luger TA, Kubin M, Schwarz T (1998) Interleukin-1 protects transformed keratinocytes from tumor necrosis factor-related apoptosis-inducing ligand. J Biol Chem 273:29247–29253
Krasteva M, Nicolas JF, Chabeau G, Garrigue JL, Bour H, Thivolet J, Schmitt D (1993) Dissociation of allergenic and immunogenic functions in contact sensitivity to para-phenylenediamine. Int Arch Allergy Immunol 102:200–204
Kubo M, Ransom J, Webb D, Hashimoto Y, Tada T, Nakayama T (1997) T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6. EMBO J 16(13):4007–4020
Kuchroo VK, Byrne MC, Atsumi Y, Greenfeld E, Connol JH, Whitters MJ, O’Hara RM, Collins M, Dorf ME (1991) T cell receptor alpha chain plays a critical role in antigen-specific suppressor cell function. Proc Natl Acad Sci USA 88:8700–8704
Kumar V, Sercarz E (1998) Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. J Immunol 161:6585–6591
Kuo CT, Leiden JM (1999) Transcriptional regulation of T lymphocyte development and function. Annu Rev Immunol 17:149–187
Lalani I, Bhol K, Ahmed AR (1997) Interleukin-10 biology, role in inflammation and autoimmunity. Ann Allergy Asthma Immunol 79:469–484
Langerhans P (1868) Über die nerven der menschlichen haut. Virchows Arch Pathol Anat 44:325–337
Lappin MB, Kimber I, Norval M (1996) The role of dendritic cells in cutaneous immunity. Arch Dermatol Res 288:109–121
Larsson A, Moller H, Björkner B, Bruze M (1997) Morphology of endogenous flare-up reactions in contact allergy to gold. Acta Derm Venereol 77:474–479
Lawrence JN, Dickson FM, Benford DJ (1997) Skin irritant-induced cytotoxicity and prostaglandin E-2 release in human skin keratinocyte cultures. Toxicol Vitro 11:627–631
Lepoittevin JP (2006) Metabolism versus chemical transformation or pro- versus prehaptens? Contact Dermatitis 54(2):73–74
Li QJ, Dinner AR, Qi S, Irvine DJ, Huppa JB, Davis MM, Chakraborty AK (2004) CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat Immunol 5:791–799
Liberato DJ, Byers VS, Ennick RG, Castagnoli N (1981) Region specific attack of nitrogen and sulfur nucleophiles on quinones from poison oak/ivy catechols (urushiols) and analogues as models for urushiol-protein conjugate formation. J Med Chem 24:28–33
Lider O, Cahalon L, Gilat D, Hershkoviz R, Siegel D, Margalit R, Shoseyov O, Cohen IR (1995) A disaccharide that inhibits tumor necrosis factor alpha is formed from the extracellular matrix by the enzyme heparinase. Proc Natl Acad Sci USA 92:5037–5041
Lonati A, Licenziati S, Marcelli M, Canaris D, Pasolini G, Caruso A, de Panfilis G (1998) Quantitative analysis “at the single cell level” of the novel CD28-CD11b- subpopulation of CD8+ T lymphocytes. ESDR meeting, Cologne
Lord GM, Matarese G, Howard LK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897–901
Luger TA (2002) Neuromediators–a crucial component of the skin immune system. J Dermatol Sci 30(2):87–93
Luger TA, Lotti T (1998) Neuropeptides: role in inflammatory skin diseases. J Eur Acad Dermatol Venereol 10:207–211
Lundeberg L, Mutt V, Nordlind K (1999) Inhibitory effect of vasoactive intestinal peptide on the challenge phase of allergic contact dermatitis in humans. Acta Derm Venereol 79:178–182
Ma J, Wing J-H, Guo Y-J, Sy M-S, Bigby M (1994) In vivo treatment with anti-ICAM-1 and antiLFA-1 antibodies inhibits contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes. Cell Immunol 158:389–399
Macatonia SE, Knight SC, Edwards AJ, Griffiths S, Fryer P (1987) Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies. J Exp Med 166:1654–1667
Marchal G, Seman M, Milon G, Truffa-Bachi P, Zilberfarb V (1982) Local adoptive transfer of skin delayed-type hypersensitivity initiated by a single T lymphocyte. J Immunol 129:954–958
Marone G, Spadaro G, Patella V, Genovese A (1994) The clinical relevance of basophil releasability. J Allergy Clin Immunol 94:1293–1303
Matura M (1998) Contact allergy to locally applied corticosteroids. Thesis, Leuven
Mayer L, Sperber K, Chan L, Child J, Toy L (2001) Oral tolerance to protein antigens. Allergy 56:12–15
Merk HF, Abel J, Baron JM, Krutmann J (2004) Molecular pathways in dermatotoxicology. Toxicol Appl Pharmacol 195:267–277
Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738
Miller SD, Sy M-S, Claman HN (1977) The induction of hapten-specific T cell tolerance using hapten-modified lymphoid membranes. II. Relative roles of suppressor T cells and clone inhibition in the tolerant state. Eur J Immunol 7:165–170
Milon G, Marchal G, Seman M, Truffa-Bachi P (1981) A delayed-type hypersensitivity reaction initiated by a single T lymphocyte. Agents Actions 11:612–614
Moed H, Boorsma DM, Stoof TJ, von Blomberg BM, Bruynzeel DP, Scheper RJ, Gibbs S, Rustemeyer T (2004a) Nickel-responding T cells are CD4+ CLA+ CD45RO+ and express chemokine receptors CXCR3, CCR4 and CCR10. Br J Dermatol 151:32–41
Moed H, Boorsma DM, Tensen CP, Flier J, Jonker MJ, Stoof TJ, Von Blomberg BM, Bruynzeel DP, Scheper RJ, Rustemeyer T, Gibbs S (2004b) Increased CCL27-CCR10 expression in allergic contact dermatitis: implications for local skin memory. J Pathol 204:39–46
Mokyr MB, Kalinichenko T, Gorelik L, Bluestone JA (1998) Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res 58:5301–5304
Morel PA, Oriss TB (1998) Crossregulation between Th1 and Th2 cells. Crit Rev Immunol 18:275–303
Morfin R, Lafaye P, Cotillon AC, Nato F, Chmielewski V, Pompon D (2000) 7 alpha-hydroxy-dehydroepiandrosterone and immune response. Ann N Y Acad Sci 917:971–982
Morgan DJ, Kreuwel HTC, Sherman LA (1999) Antigen concentration and precursor frequency determine the rate of CD8(+) T cell tolerance to peripherally expressed antigens. J Immunol 163:723–727
Morris DL (1998) Intradermal testing and sublingual in desensitization for nickel. Cutis 61:129–132
Moser B, Loetscher M, Piali L, Loetscher P (1998) Lymphocyte responses to chemokines. Int Rev Immunol 16:323–3244
Moser K, Kriwet K, Naik A, Kalia YN, Guy RH (2001) Passive skin penetration enhancement and its quantification in vitro. Eur J Pharm Biopharm 52:103–112
Moulon C, Vollmer J, Weltzien H-U (1995) Characterization of processing requirements and metal crossreactivities in T cell clones from patients with allergic contact dermatitis to nickel. Eur J Immunol 25:3308–3315
Mucida D, Salek-Ardakani S (2009) Regulation of TH17 cells in the mucosal surfaces. J Allergy Clin Immunol 123(5):997–1003
Murphy K, Travers P, Walport M (eds) (2008) Janeway’s immunobiology, 7th edn. Garland Science/Taylor & Francis Group, New York/Oxford
Mutschler J, Giménez-Arnau E, Foertsch L, Gerberick GF, Lepoittevin JP (2009) Mechanistic assessment of peptide reactivity assay to predict skin allergens with Kathon CG isothiazolinones. Toxicol In Vitro 23(3):439–446
Nagira M, Imai T, Hieshima K, Kusuda J, Ridanpaa M, Takagi S, Nishimura M, Kakizaki M, Nomiyama H, Yoshie O (1997) Molecular cloning of a novel human CC chemokine secondary lymphoid-tissue chemokine that is a potent chemoattractant for lymphocytes and mapped to chromosome 9p13. J Biol Chem 272:19518–19524
Naisbitt DJ (2004) Drug hypersensitivity reactions in skin: understanding mechanisms and the development of diagnostic and predictive tests. Toxicology 194:179–196
Nakamura T, Kamogawa Y, Bottomly K, Flavell RA (1997a) Polarization of IL-4- and IFN-gamma-producing CD4(+) T cells following activation of naive CD4(+) T cells. J Immunol 158:1085–1094
Nakamura T, Lee RK, Nam SY, Podack ER, Bottomly K, Flavell RA (1997b) Roles of IL-4 and IFN-g in stabilizing the T helper cell type-1 and 2 phenotype. J Immunol 158:2648–2653
Nataf S, Davoust N, Ames RS, Barnum SR (1999) Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol 162:4018–4023
Ngo VN, Tang LH, Cyster JG (1998) Epstein-Barr virus-induced molecule 1 ligand chemokine is expressed by dendritic cells in lymphoid tissues and strongly attracts naïve T cells and activated B cells. J Exp Med 188:181–191
O’Garra A (1998) Cytokines induce the development of functionally heterogeneous T helper cell subsets. Immunity 8:275–283
Ohshima Y, Tanaka Y, Tozawa H, Takahashi Y, Maliszewski C, Delespesse C (1997) Expression and function of OX40 ligand on human dendritic cells. J Immunol 159:3838–3848
Orange JS, Biron CA (1996) An absolute and restricted requirement for IL-12 in natural killer cell IFN-g production and antiviral defense. J Immunol 156:1138–1142
Orteu CH, Poulter LW, Rustin MHA, Sabin CA, Salmon M, Akbar AN (1998) The role of apoptosis in the resolution of T cell-mediated cutaneous inflammation. J Immunol 161:1619–1629
Oukka M (2008) Th17 cells in immunity and autoimmunity. Ann Rheum Dis 67(Suppl 3):iii26–iii29
Ozawa H, Nakagawa S, Tagami H, Aiba S (1996) Interleukin-1b and granulocyte-macrophage colony stimulating factor mediate Langerhans cell maturation differently. J Invest Dermatol 106:441–445
Panzani RC, Schiavino D, Nucera E, Pellegrino S, Fais G, Schinco G, Patriarca G (1995) Oral hyposensitization to nickel allergy: preliminary clinical results. Int Arch Allergy Immunol 107:251–254
Park SH, Chiu YH, Jayawardena J, Roark J, Kavita U, Bendelac A (1998) Innate and adaptive functions of the CD1 pathway of antigen presentation. Semin Immunol 10:391–398
Patlewicz GY, Basketter DA, Pease CK, Wilson K, Wright ZM, Roberts DW, Bernard G, Arnau EG, Lepoittevin JP (2004) Further evaluation of quantitative structure–activity relationship models for the prediction of the skin sensitization potency of selected fragrance allergens. Contact Dermatitis 50:91–97
Perez VL, Lederer JA, Lichtman AH, Abbas AK (1995) Stability of Th1 and Th2 populations. Int Immunol 7:869–875
Piccirillo CA, Thornton AM (2004) Cornerstone of peripheral tolerance: naturally occurring CD4+ CD25+ regulatory T cells. Trends Immunol 25:374–380
Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MA Jr (1986) Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 136:1680–1687
Polak L (1980) Immunological aspects of contact sensitivity. An experimental study. Monogr Allergy 15:4–60
Polak L, Rinck C (1978) Mechanism of desensitization in DNCH-contact sensitive guinea pigs. J Invest Dermatol 70:98–104
Polak L, Turk JL (1968a) Studies on the effect of systemic administration of sensitizers in guinea-pigs with contact sensitivity to inorganic metal compounds. II. The flare-up of previous test sites of contact sensitivity and the development of a generalized rash. Clin Exp Immunol 3:253–262
Polak L, Turk SL (1968b) Studies on the effect of systemic administration of sensitizers in guinea pigs with contact sensitivity to inorganic metal compounds. I. The induction of immunological unresponsiveness in already sensitized animals. Clin Exp Immunol 3:245–251
Price AA, Cumberbatch M, Kimber I (1997) α6 integrins are required for Langerhans cell migration from the epidermis. J Exp Med 186:1725–1735
Probst P, Küntzlin D, Fleischer B (1995) TH2-type infiltrating T cells in nickel-induced contact dermatitis. Cell Immunol 165:134–140
Pulendran B (2004) Modulating TH1/TH2 responses with microbes, dendritic cells, and pathogen recognition receptors. Immunol Res 29:187–196
Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ (2004) CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307–328
Rambukhana A, Bos JD, Irik D, Menko WJ, Kapsenberg ML, Das PK (1995) In situ behaviour of human Langerhans cells in skin organ culture. Lab Invest 73:521–531
Randolph GJ (2001) Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. Semin Immunol 13:267–274
Redegeld FA, Nijkamp FP (2003) Immunoglobulin free light chains and mast cells: pivotal role in T-cell-mediated immune reactions? Trends Immunol 24:181–185
Richters CD, Hoekstra MJ, van Baare J, Du Pont JS, Hoefsmit EC, Kamperdijk EW (1994) Isolation and characterization of migratory human skin dendritic cells. Clin Exp Immunol 98:330–336
Robbiani DF, Finch RA, Jager D, Muller WA, Sartorelli AC, Randolph GJ (2000) The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell 103:757–768
Roberts DW, Lepoittevin J-P (1998) Allergic contact dermatitis: the molecular basis. In: Lepoittevin J-P, Basketter DA, Goossens A, Karlberg A-T (eds) Springer, Berlin/Heidelberg/New York, pp 81–1118
Rogge L, Barberis-Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F (1997) Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185:825–831
Romagnani S (2006) Regulation of the T cell response. Clin Exp Allergy 36(11):1357–1366
Romani N, Holzmann S, Tripp CH, Koch F, Stoitzner P (2003) Langerhans cells – dendritic cells of the epidermis. Acta Pathol Microbiol Immunol Scand 111:725–740
Ross R, Gilitzer C, Kleinz R, Schwing J, Kleinert H, Forstermann U, Reske-Kunz AB (1998) Involvement of NO in contact hypersensitivity. Int Immunol 10:61–69
Rothenberg ME (2010) Innate sensing of nickel. Nat Immunol 11(9):781–782
Rowe A, Bunker CB (1998) Interleukin-4 and the interleukin-4 receptor in allergic contact dermatitis. Contact Dermatitis 38:36–39
Rowe A, Farrell AM, Bunker CB (1997) Constitutive endothelial and inducible nitric oxide synthase in inflammatory dermatoses. Br J Dermatol 136:18–23
Rustemeyer T, von Blomberg BME, de Ligter S, Frosch PJ, Scheper RJ (1999) Human T lymphocyte priming in vitro by haptenated autologous dendritic cells. Clin Exp Immunol 117:209–216
Rustemeyer T, de Groot J, von Blomberg BME, Frosch PJ, Scheper RJ (2001) Induction of tolerance and cross-tolerance to methacrylate contact sensitizers. Toxicol Appl Pharmacol 176:195–202
Rustemeyer T, de Groot J, von Blomberg BME, Frosch PJ, Scheper RJ (2002) Assessment of contact allergen cross-reactivity by retesting. Exp Dermatol 11:257–265
Rustemeyer T, von Blomberg BME, van Hoogstraten IMW, Bruynzeel DP, Scheper RJ (2004) Analysis of effector and regulatory immune-reactivity to nickel. Clin Exp Allergy 34(9):1458–1466
Saeki H, Moore AM, Brown MJ, Hwan ST (1999) Secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes. J Immunol 162:2472–2475
Saint-Mezard P, Krasteva M, Chavagnac C, Bosset S, Akiba H, Kehren J, Kanitakis J, Kaiserlian D, Nicolas JF, Berard F (2003) Afferent and efferent phases of allergic contact dermatitis (ACD) can be induced after a single skin contact with haptens: evidence using a mouse model of primary ACD. J Invest Dermatol 120:641–647
Sallusto F, Lanzavecchia A, Mackay CR (1998a) Chemokines and chemokine receptors in T-cell priming and Th1/Th2-mediated responses. Immunol Today 19:568–574
Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR, Qin S, Lanzavecchia A (1998b) Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation. Eur J Immunol 28:2760–2769
Sallusto F, Palermo B, Lenig D, Miettinen M, Matikainen S, Julkunen I, Forster R, Burgstahler R, Lipp M, Lanzavecchia A (1999) Distinct patterns and kinetics of chemokine production regulate dendritic cell function. Eur J Immunol 29:1617–1625
Sallusto F, Geginat J, Lanzavecchia A (2004) Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol 22:745–763
Scheper RJ, von Blomberg BME, Boerrigter GH, Bruynzeel D, van Dinther A, Vos A (1983) Induction of local memory in the skin. Role of local T cell retention. Clin Exp Immunol 51:141–148
Scheper RJ, van Dinther-Janssen AC, Polak L (1985) Specific accumulation of hapten-reactive T cells in contact sensitivity reaction sites. J Immunol 134:1333–1336
Schmidt M, Raghavan B, Müller V, Vogl T, Fejer G, Tchaptchet S, Keck S, Kalis C, Nielsen PJ, Galanos C, Roth J, Skerra A, Martin SF, Freudenberg MA, Goebeler M (2010) Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel. Nat Immunol 11(9):814–819
Schnuch A, Westphal GA, Muller MM, Schulz TG, Geier J, Brasch J, Merk HF, Kawakubo Y, Richter G, Koch P, Fuchs T, Gutgesell T, Reich K, Gebhardt M, Becker D, Grabbe J, Szliska C, Aberer W, Hallier E (1998) Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients with contact allergy. Contact Dermatitis 38:209–211
Schoenberger SP, Toes REM, Vandervoort EIH, Offringa R, Melief CJM (1998) T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 393:480–483
Schon MP, Zollner TM, Boehncke WH (2003) The molecular basis of lymphocyte recruitment to the skin: clues for pathogenesis and selective therapies of inflammatory disorders. J Invest Dermatol 121:951–962
Schuler G, Steinman RM (1985) Murine epidermal Langerhans cells mature into potent immune-stimulatory dendritic cells in vitro. J Exp Med 161:526–546
Schwarz A, Grabbe S, Riemann H, Aragane Y, Simon M, Manon S, Andrade S, Luger TA, Zlotnik A, Schwarz T (1994) In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol 103:211–216
Schwarzenberger K, Udey MC (1996) Contact allergens and epidermal proinflammatory cytokines modulate Langerhans cell E-cadherin expression in situ. J Invest Dermatol 106:553–558
Seiffert K, Granstein RD (2006) Neuroendocrine regulation of skin dendritic cells. Ann N Y Acad Sci 1088(1):195–206
Semma M, Sagami S (1981) Induction of suppressor T cells to DNFB contact sensitivity by application of sensitizer through Langerhans cell-deficient skin. Arch Dermatol Res 271:361–364
Shimizu Y, Newman W, Gopal TV, Horgan KJ, Graber N, Beall LD, van Seventer GA, Shaw S (1991) Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions. J Cell Biol 113:1203–1212
Shirakawa T, Kusaka Y, Morimoto K (1992) Specific IgE antibodies to nickel in workers with known reactivity to cobalt. Clin Exp Allergy 22:213–218
Shreedhar V, Giese T, Sung VW, Ullrich SE (1998) A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression. J Immunol 160:3783–3789
Silberberg-Sinakin I, Thorbecke GJ, Baer RL, Rosenthal SA, Berezowsky V (1976) Antigen-bearing Langerhans cells in skin, dermal lymphatics, and in lymph nodes. Cell Immunol 25:137–151
Skog E (1976) Spontaneous flare-up reactions induced by different amounts of 1,3-dinitro-4-chlorobenzene. Acta Derm Venereol 46:386–395
Steinbrink K, Jonuleit H, Muller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93:1634–1642
Steinman RM, Hoffman L, Pope M (1995) Maturation and migration of cutaneous dendritic cells. J Invest Dermatol 105:2S–7S
Sterry W, Künne N, Weber-Matthiesen K, Brasch J, Mielke V (1991) Cell trafficking in positive and negative patch test reactions: demonstration of a stereotypic migration pathway. J Invest Dermatol 96:459–462
Stingl G, Katz SI, Clement L, Green I, Shevach EM (1978) Immunological functions of Ia-bearing epidermal Langerhans cells. J Immunol 121:2005–2013
Streilein JW, Grammer SF (1989) In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. J Immunol 143:3925–3933
Strobel S, Mowat AM (1998) Immune responses to dietary antigens: oral tolerance. Immunol Today 19:173–181
Szepietowski JC, McKenzie RC, Keohane SG, Walker C, Aldridge RD, Hunter JA (1997) Leukaemia inhibitory factor: induction in the early phase of allergic contact dermatitis. Contact Dermatitis 36:21–25
Taams LS, van Rensen AJML, Poelen MC, van Els CACM, Besseling AC, Wagenaar JPA, van Eden W, Wauben MHM (1998) Anergic T cells actively suppress T cell responses via the antigen presenting cell. Eur J Immunol 28:2902–2912
Taams LS, van Eden W, Wauben MHM (1999) Dose-dependent induction of distinct anergic phenotypes: multiple levels of T cell anergy. J Immunol 162:1974–1981
Taams LS, Boot EPJ, van Eden W, Wauben MHM (2000) ‘Anergic’ T cells modulate the T-cell activating capacity of antigen-presenting cells. J Autoimmun 14:335–341
Takatori H, Kanno Y, Chen Z, O’Shea JJ (2008) New complexities in helper T cell fate determination and the implications for autoimmune diseases. Mod Rheumatol 18(6):533–541
Tammaro A, De Marco G, Persechino S, Narcisi A, Camplone G (2009) Allergy to nickel: first results on patients administered with an oral hyposensitization therapy. Int J Immunopathol Pharmacol 22(3):837–840
Tang A, Amagai M, Granger LG, Stanley JR, Udey MC (1993) Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin. Nature 361:82–85
Toebak MJ, Moed H, von Blomberg MB, Bruynzeel DP, Gibbs S, Scheper RJ, Rustemeyer T (2006) Intrinsic characteristics of contact and respiratory allergens influence production of polarizing cytokines by dendritic cells. Contact Dermatitis 55(4):238–245
Trautmann A, Randriamampita C (2003) Initiation of TCR signalling revisited. Trends Immunol 24:425–428
Tsuji RF, Geba GP, Wang Y, Kawamoto K, Matis LA, Askenase PW (1997) Required early complement activation in contact sensitivity with generation of local C5-dependent chemotactic activity, and late T cell interferon g: a possible initiating role of B cells. J Exp Med 186:1015–1026
Turk JL (1975) Delayed hypersensitivity, 2nd edn. North-Holland, Amsterdam
Ulrich P, Grenet O, Bluemel J, Vohr HW, Wiemann C, Grundler O, Suter W (2001) Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen. Arch Toxicol 75(8):470–479
Uotila P (1996) The role of cyclic AMP and oxygen intermediates in the inhibition of cellular immunity in cancer. Cancer Immunol Immunother 43:1–9
van Beelen AJ, Teunissen MB, Kapsenberg ML, de Jong EC (2007) Interleukin-17 in inflammatory skin disorders. Curr Opin Allergy Clin Immunol 7(5):374–381
van de Ven R, Scheffer GL, Scheper RJ, de Gruijl TD (2009) The ABC of dendritic cell development and function. Trends Immunol 30(9):421–429
Van Hoogstraten IMW, Andersen JE, von Blomberg BME, Boden D, Bruynzeel DP, Burrows D, Camarasa JMG, Dooms-Goossens A, Lahti A, Menné T, Rycroft R, Todd D, Vreeburg KJJ, Wilkinson JD, Scheper RJ (1989) Preliminary results of a multicenter study on the incidence of nickel allergy in relationship to previous oral and cutaneous contacts. In: Frosch PJ, Dooms-Goossens A, Lachapelle JM, Rycroft RJG, Scheper RJ (eds) Current topics in contact dermatitis. Springer, Berlin/Heidelberg/New York, pp 178–184
Van Hoogstraten IMW, von Blomberg BME, Boden D, Kraal G, Scheper RJ (1994) Non-sensitizing epicutaneous skin tests prevent subsequent induction of immune tolerance. J Invest Dermatol 102:80–83
Van Loweren H, Meade R, Askenase PW (1983) An early component of delayed type hypersensitivity mediated by T cells and mast cells. J Exp Med 157:1604–1617
Vestweber D, Blanks JE (1999) Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213
Vieira PL, Kalinski P, Wierenga EA, Kapsenberg ML, Dejong EC (1998) Glucocorticoids inhibit bioactive IL-12P70 production by in vitro-generated human dendritic cells without affecting their T cell stimulatory potential. J Immunol 161:5245–5251
Viola A, Lanzavecchia A (1996) T cell activation determined by T cell receptor number and tunable thresholds. Science 273:104–106
Virag L, Szabo E, Bakondi E, Bai P, Gergely P, Hunyadi J, Szabo C (2002) Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. Exp Dermatol 11:189–202
Von Andrian UH, Mrini C (1998) In situ analysis of lymphocyte migration to lymph nodes. Cell Adhes Commun 6:85–96
von Blomberg BME, Bruynzeel DP, Scheper RJ (1991) Advances in mechanisms ofallergic contact dermatitis: in vitro and in vivo research. In: Marzulli FN, Maibach HI (eds) Dermatotoxicology, 4th edn. Hemisphere Publishing Corporation, New York, pp 255–362
von Herrath MG (1997) Bystander suppression induced by oral tolerance. Res Immunol 148:541–554
Waldorf HA, Walsh LJ, Schechter NM, Murphy GF (1991) Early molecular events in evolving cutaneous delayed hypersensitivity in humans. Am J Pathol 138:477–486
Walker C, Kristensen F, Bettens F, deWeck AL (1983) Lymphokine regulation of activated (G1) lymphocytes. I. Prostaglandin E2-induced inhibition of interleukin 2 production. J Immunol 130:1770–1773
Walsh LJ, Lavker RM, Murphy GF (1990) Determinants of immune cell trafficking in the skin. Lab Invest 63:592–600
Wang B, Esche C, Mamelak A, Freed I, Watanabe H, Sauder DN (2003) Cytokine knockouts in contact hypersensitivity research. Cytokine Growth Factor Rev 14:381–389
Wardorf HA, Walsh LJ, Schechter NM (1991) Early cellular events in evolving cutaneous delayed hypersensitivity in humans. Am J Pathol 138:477–486
Weigle WO, Romball CG (1997) CD4+ T-cell subsets and cytokines involved in peripheral tolerance. Immunol Today 18:533–538
Weiner HL (1997) Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 18:335–343
Weiner HL, Gonnella PA, Slavin A, Maron R (1997) Oral tolerance: cytokine milieu in the gut and modulation of tolerance by cytokines. Res Immunol 148:528–533
Weinlich G, Heine M, Stössel H, Zanella M, Stoitzner P, Ortner U, Smolle J, Koch F, Sepp NT, Schuler G, Romani N (1998) Entry into afferent lymphatics and maturation in situ of migrating murine cutaneous dendritic cells. J Invest Dermatol 110:441–448
Weiss JM, Sleeman J, Renkl AC, Dittmar H, Termeer CC, Taxis S, Howells N, Hofmann M, Kohler G, Schöpf E, Ponta H, Herrlich P, Simon JC (1997) An essential role for CD44 variant isoforms in epidermal Langerhans cell and blood dendritic cell function. J Cell Biol 137:1137–1147
Wendel GD, Stark BJ, Jamison RB, Molina RD, Sullivan TJ (1985) Penicillin allergy and desensitization in serious infections during pregnancy. N Engl J Med 312:1229–1232
Werfel T, Hentschel M, Kapp A, Renz H (1997) Dichotomy of blood- and skin-derived IL-4-producing allergen-specific T cells and restricted V beta repertoire in nickel-mediated contact dermatitis. J Immunol 158:2500–2505
Weston MC, Peachell PT (1998) Regulation of human mast cell and basophil function by cAMP. Gen Pharmacol 31:715–719
Wilkinson SM, Mattey DL, Beck MH (1994) IgG antibodies and early intradermal reactions to hydrocortisone in patients with cutaneous delayed-type hypersensitivity to hydrocortisone. Br J Dermatol 131:495–498
Willis CM, Young E, Brandon DR, Wilkinson JD (1986) Immunopathological and ultrastructural findings in human allergic and irritant contact dermatitis. Br J Dermatol 115:305–316
Wilson NS, Villadangos JA (2004) Lymphoid organ dendritic cells: beyond the Langerhans cells paradigm. Immunol Cell Biol 82:91–98
Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM, Choi YW (1997) TRANCE (Tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor. J Exp Med 186:2075–2080
Wu K, Bi Y, Sun K, Wang C (2007) IL-10-producing type 1 regulatory T cells and allergy. Cell Mol Immunol 4(4):269–275
Yu X, Barnhill RL, Graves DT (1994) Expression of monocyte chemoattractant protein-1 in delayed type hypersensitivity reactions in the skin. Lab Invest 71:226–235
Zembala M, Ashershon GL (1973) Depression of T cell phenomenon of contact sensitivity by T cells from unresponsive mice. Nature 244:227–228
Zhang ZY, Michael JG (1990) Orally inducible immune unresponsiveness is abrogated by IFN-gamma treatment. J Immunol 144:4163–4165
Zhang X, Brunner T, Carter L, Dutton RW, Rogers P, Bradley L, Sato T, Reed JC, Green D, Swain SL (1997) Unequal death in T helper cell (Th)1 and Th2 effectors: Th1, but not Th2, effectors undergo rapid Fas/FasL-mediated apoptosis. J Exp Med 185:1837–1849
Zhou L, Littman DR (2009) Transcriptional regulatory networks in Th17 cell differentiation (review). Curr Opin Immunol 21(2):146–152
Zhou L, Chong MM, Littman DR (2009) Plasticity of CD4+ T cell lineage differentiation (review). Immunity 30(5):646–655, PubMed PMID: 19464987
Zinkernagel RM (2004) On ‘reactivity’ versus ‘tolerance’. Immunol Cell Biol 82:343–352
Zlotnik A, Morales J, Hedrick JA (1999) Recent advances in chemokines and chemokine receptors. Crit Rev Immunol 19:1–47
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this entry
Cite this entry
Rustemeyer, T., van Hoogstraten, I.M.W., von Blomberg, B.M.E., Scheper, R.J. (2012). Mechanisms of Allergic Contact Dermatitis. In: Rustemeyer, T., Elsner, P., John, SM., Maibach, H.I. (eds) Kanerva's Occupational Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-02035-3_14
Download citation
DOI: https://doi.org/10.1007/978-3-642-02035-3_14
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-02034-6
Online ISBN: 978-3-642-02035-3
eBook Packages: MedicineReference Module Medicine