Abstract
Until comparatively recently, allergic (atopic) disease was viewed as a manifestation of hyperreactivity to essentially non-pathogenic soluble protein antigens which are ubiquitous in the natural environment. In this context, normality would equate to non-responsiveness, resulting from either tolerance or ignorance of the antigens. However, it is now clear (reviewed inc[1]) that active T cell immunity to at least one class of these antigens (airborne ”inhalant“ allergens) is essentially universal amongst adults, clinical reactivity being a function of the cytokine profiles of CD4+ Th-cells which dominate relevant Th-memory populations. Thus, atopics who respond to allergen exposure via IgE production, eosinophilia etc., manifest Th-2-skewed memory, whereas T cell memory in non-responsive normal adults is dominated by Th- I -cytokines such as IFNγ. The situation with respect to ingested environmental allergens (ubiquitous in the diet) appears both qualitatively and quantitatively different, as T cell reactivity to this class of antigens is considerably less frequent in the adult population1.2.
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References
Holt PG. Immunoprophylaxis of atopy: light at the end of the tunnel? Immunol Today 1994; 15: 484–9.
Holt PG, O’Keeffe PO, Holt BJ, Upham JW, Baron-Hay MJ, Suphioglu C, Knox B, Stewart GA, Thomas WR, Sly PD. T-cell “priming” against environmental allergens in human neonates: sequential deletion of food antigen specificities during infancy with concomitant expansion of responses to ubiquitous inhalant allergens. Ped Allergy Immunol 1995; 6: 85–90.
Sedgwick JD, Holt PG. Induction of IgE-secreting cells and IgE isotype-specific suppressor T cells in the respiratory lymph nodes of rats in response to antigen inhalation. Cell Immunol 1985; 94: 182–94.
McMenamin C, Holt PG. The natural immune response to inhaled soluble protein antigens involves major histocompatibility complex (MHC) class I-restricted CD8+ T cell-mediated but MHC class II-restricted CD4+ T cell-dependent immune deviation resulting in selective suppression of IgE production. 1 Exp Med 1993; 178: 889–99.
McMenamin C, Pimm C, McKersey M, Holt PG. Regulation of CD4’-TH-2-dependent IgE responses to inhaled antigen in mice by antigen-specific y/6 T-cells. Science 1994; 265: 1859–1861.
McMenamin C, McKersey M, Kuhnlein P, Hunig T, Holt PG. y/6 T-cells downregulate primary IgE responses in rats to inhaled soluble protein antigens. J Immunol 1995; 154: 4390–94.
Thomas WR, Cooper D, Holt PG. Immunity at body surfaces. The Immunologist 1995; 3: 130–132.
Friedman A, Weiner HL. Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc. Natl. Acad. Science, USA1994; 91: 6688–92.
Strobel S, Ferguson A. Immune responses to fed protein antigens in mice. 3. Systemic tolerance or priming is related to age at which antigen is first encountered. Pediatr Res 1984; 18: 588–94.
Mariani F, Price JF, Kemeny DM. The IgG subclass antibody response to an inhalant antigen (Dermatophagoides pteronyssinus) during the first year of life: evidence for early stimulation of the immune system following natural exposure. Clin Exp Allergy 1992; 22: 29–33.
Hattevig G, Kjellman B, Bjerkstén B. Appearance IgE antibodies to ingested and inhaled allergens during the first 12 years of life in atopic and non-atopic children. Ped Allergy Immunol 1993; 4: 182–6.
Holt PG. Primary allergic sensitisation to environmental antigens: perinatal T-cell priming as a determinant of responder phentotype in adulthood. J Exp Med 1996; 183: 1297–1301.
Yabuhara A, Macaubas C, Prescott SL, Venaille T, Holt BJ, Habre W, Sly PD, Holt PG. Th-2-polarised immunological memory to inhalant allergens in atopics is established during infancy and early childhood. Clin Exp Allergy Submitted:
Wegmann TG, Lin H. Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationshiip: is successful pregnancy a Th2 phenomenon? Immunol Today 1993; 14: 353–56.
Krishnan L, Guilbert LJ, Wegmann TG, Belosevic M, Mosmann TR. T helper 1 response against Leishmania major in pregnant C57BL/6 mice increases implantation failure and fetal resportions. J Immunol 1996; 156: 653–62.
Chen N. Gao Q, Field EH. Expansion of memory Th2 cells over Thl cells in neonatal primed mice. Transplantation 1995; 60: 1187–93.
Holt PG. Postnatal maturation of immune competence during infancy and early childhood. Pediatr Allergy Immunol 1995; 6: 59–70.
Holt PG, Clough JB. Holt BJ, Baron-Hay MJ. Rose AH, Robinson BWS, Thomas WR. Genetic `risk’ for atopy is associated with delayed postnatal maturation of T-cell competence. Clin Exp Allergy 1992; 22: 1093–9.
Warner JA, Miles EA. Jones AC. Quint DJ, Colwell BM, Warner JO. Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema? Clin Exp Allergy 1994; 24: 423–30.
Tang MLK, Kemp AS, Thorburn J, Hill DJ. Reduced interferon-y secretion in neonates and subsequent atopy. Lancet 1994: 344: 983–86.
Rinas U, Horneff G, Wahn V. Interferon-y production by cord-blood mononuclear cells is reduced in newborns with a family history of atopic disease and is independent from cord blood IgE-levels. Pediatr Allergy Immunol 1993; 4: 60–4.
Singh RR, Hahn BH, Sercarz EE. Neonatal peptide exposure can prime T cells, and upon subsequent immunization induce their immune deviation: implications for antibody vs. T cell-mediated autoimmunity. J Exp Med 1996; 183: 1613–1622.
Ridge JP, Fuchs EJ, Matzinger P. Neonatal tolerance revisited: turning on newborn T cells with dendritic cells. Science 1996; 271: 1723–1726.
Schon-Hegrad MA, Oliver J, McMenamin PG, Holt PG. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (la)-bearing dendritic cells (DC) in the conducting airways. J Exp Med 1991; 173: 1345–56.
Holt PG, Haining S, Nelson DJ, Sedgwick JD. Origin and steady-state turnover of class I1 MHC-bearing Dendritic Cells in the epithelium of the conducting airways. J Immunol 1994; 153: 256–61.
Nelson DJ, McMenamin C, McWilliam AS, Brenan M, Holt PG. Development of the airway intraepithelial Dendritic Cell network in the rat from class II MHC (la) negative precursors: differential regulation of la expression at different levels of the respiratory tract. J Exp Med 1994; 179: 203–12.
Nelson DJ, Holt PG. Defective regional immunity in the respiratory tract of neonates is attributable to hyporesponsiveness of local Dendritic Cells to activation signals. J Immunol 1995; 155: 3517–3524.
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Holt, P.G., Macaubas, C., Cooper, D., Nelson, D.J., Mcwilliam, A.S. (1997). Th-1/Th-2 Switch Regulation in Immune Responses to Inhaled Antigens. In: Ricciardi-Castagnoli, P. (eds) Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology, vol 417. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9966-8_49
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DOI: https://doi.org/10.1007/978-1-4757-9966-8_49
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