T-Cells in the Pathogenesis of Asthma and Allergic Diseases

  • Marc Humbert
  • Stephen R. Durham


T-cells have a central role to play in an antigen-driven inflammatory process, since they are the only cells capable of recognizing antigenic material after processing by antigen presenting cells. CD4+ and CD8+ T lymphocytes activated in this manner elaborate a wide variety of protein mediators, including cytokines, which have the capacity to orchestrate the differentiation, recruitment, accumulation, and activation of specific granulocytes at mucosal surfaces. T-cell derived products can also influence immunoglobulin production by plasma cells. There now exists considerable support for the hypothesis that allergic diseases and asthma represent specialized forms of cell-mediated immunity, in which cytokines secreted predominantly by activated T-cells but also by other leukocytes such as mast cells and eosinophils bring about the specific accumulation and activation of eosinophils. This observation has important implications for future therapeutic procedures since it suggests that drugs modulating T-lymphocyte function may be of considerable interest in allergic conditions and asthma. This chapter summarizes the possible role of T-cells in allergic diseases and possible therapeutic manipulation of inappropriate T-cell activation in humans.


Major Histocompatibility Complex Class Allergic Disease Allergy Clin Immunol Allergic Inflammation Immunol Today 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Germain RN (1993) Antigen processing and presentation. In: Paul WE, ed. Fundamental Immunology, 3rd ed. Raven, New York, pp. 629–676.Google Scholar
  2. 2.
    Mossmann TR, Coffman RL (1987) Two types of mouse helper T cell clone: implication for immune regulation. Immunol Today 8: 223–227.Google Scholar
  3. 3.
    Mossmann TR, Sad S (1996) The expanding universe of T-cell subsets: Thl, Th2 and more. Immunol Today 17: 138–146.Google Scholar
  4. 4.
    Romagnani S (1994) Lymphokine production by human T cells in disease states. Annu Rev Immunol 12: 227–257.PubMedGoogle Scholar
  5. 5.
    Maneti R, Parronchi P, Giudzi MG, et al. (1993) Natural killer cell stimulating factor (interleukin 12) (IL-12) induces T helper type 1 (TH1) specific immune responses and inhibits development of IL-4 producing TH cells. J Exp Med 177: 1199–1204.Google Scholar
  6. 6.
    Trinchieri G (1994) Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes. Blood 84: 4008–4024.PubMedGoogle Scholar
  7. 7.
    Parronchi P, Manetti R, Simonelli C, et al. (1991) Cytokine production by allergen (Der pI)-specific CD4+ T cell clones derived from a patient with severe atopic disease. Int J Clin Lab Res 21: 186–189.PubMedGoogle Scholar
  8. 8.
    Robinson DS, Hamid Q, Ying S, et al. (1992) Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma N Engl J Med 326: 298–304.Google Scholar
  9. 9.
    Humbert M, Durham SR, Kimmitt P, et al. (1996) Relationship between bronchial mucosal IL-5 mRNA expression with disease severity in atopic asthma. Am J Respir Crit Care Med 153: A217 (abstract).Google Scholar
  10. 10.
    Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR (1997) Relationship between bronchial mucosal interleukin-4 and interleukin-5 expression and disease severity in atopic asthma. Am J Resp Crit Care Med 156: 704–708.PubMedGoogle Scholar
  11. 11.
    Ying S, Durham SR, Jacobson MR, Rak S, Masuyama K, Lowhagen O, Kay AB, Hamid Q (1994) T-lymphocytes and mast cells express messenger RNA for interleukin-4 in the nasal mucosa in allergen-induced rhinitis. Immunology 82: 200–204.PubMedGoogle Scholar
  12. 12.
    Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB (1995) Phenotype of cells expressing mRNA for TH2-type (interleukin-4 and interleukin-5) and TH1-type (interleukin-2 and interferon-gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatics and normal control subjects. Am J Respir Cell Mol Biol 12: 477–487.PubMedGoogle Scholar
  13. 13.
    Till S, Li B, Durham S, et al. (1995) Secretion of the eosinophil-active cytokines (IL-5, GM-CSF and IL-3) by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics and atopic and nonatopic controls. Eur J Immunol 25: 2727–2731.PubMedGoogle Scholar
  14. 14.
    Frew AJ, Kay AB (1988) The relationship between infiltrating CD4+ lymphocytes, activated eosinophils, and the magnitude of the allergen-induced late-phase cutaneous reaction in man J Immunol 141: 4158–4164.Google Scholar
  15. 15.
    Ying S, Taborda-Barata L, Meng Q, Humbert M, Kay AB (1995) The kinetics of allergen-induced transcription of messenger RNA for monocyte chemotactic protein-3 and RANTES in the skin of human atopic subjects: relationship to eosinophil, T-cell, and macrophage recruitment. J Exp Med 181: 2153–2159.Google Scholar
  16. 16.
    Kay AB, Ying S, Varney V, et al. (1991) Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5 and granulocyte/macrophage colony stimulating-factor, in allergen-induced late-phase reactions in atopic subjects. J Exp Med 173: 775–778.PubMedGoogle Scholar
  17. 17.
    Varney VA, Jacobson MR, Sudderick RM, et al. (1992) Immunohistology of the nasal mucosa following allergen-induced rhinitis: identification of activated T lymphocytes, eosinophils and neutrophils. Am Rev Respir Dis 145: 170–175.Google Scholar
  18. 18.
    Lim MC, Taylor RM, Naclerio RM (1995) The histology of allergic rhinitis and its comparison to cellular changes in nasal lavage. Am J Respir Crit Care Med 151: 136–144.PubMedGoogle Scholar
  19. 19.
    Hamid Q, Barkans J, Robinson DS, Durham SR, Kay AB (1992) Co-expression of CD25 and CD3 in atopic allergy and asthma. Immunology 75: 659–663.PubMedGoogle Scholar
  20. 20.
    Durham SR, Ying S, Varney V, et al. (1992) Cytokine messenger RNA expression for IL-3, IL-4, IL-5 and GM-CSF in the nasal mucosa after local allergen provocation: relationship to tissue eosinophilia. J Immunol 148: 2390–2394.PubMedGoogle Scholar
  21. 21.
    Bradding PL, Feather IH, Howarth PH, et al. (1992) Interleukin 4 is localised to and released by human mast cells. J Exp Med 176: 1381–1386.PubMedGoogle Scholar
  22. 22.
    Sim TC, Reece LM, Hilsmeier KA, Grant JA, Allam R (1995) Secretion of chemokines and other cytokines in allergen-induced nasal responses: inhibition by topical steroid treatment. Am J Respir Crit Care Med 152: 927–933.PubMedGoogle Scholar
  23. 23.
    Bousquet J, Chanez P, Lacoste J-Y, et al. (1990) Eosinophilic inflammation in asthma. N Engl J Med 323: 1033–1039.PubMedGoogle Scholar
  24. 24.
    Azzawi M, Bradley B, Jeffery PK et al. (1990) Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis 142: 1407–1413.PubMedGoogle Scholar
  25. 25.
    Djukanovic R, Wilson JW, Britten KM (1990) Mucosal inflammation in asthma. Am Rev Respir Dis 142: 434–457.PubMedGoogle Scholar
  26. 26.
    Corrigan CJ, Kay AB (1992) T cells and eosinophils in the pathogenesis of asthma. Immunol Today 13: 501–507.PubMedGoogle Scholar
  27. 27.
    Walker C, Kaegi MK, Braun P, Blaser K (1991) Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol 88: 935–942.PubMedGoogle Scholar
  28. 28.
    Robinson DS, Bentley AM, Hartnell A, Kay AB, Durham SR (1993) Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: relation to asthma symptoms, lung function, and bronchial responsiveness. Thorax 48: 26–32.PubMedGoogle Scholar
  29. 29.
    Gonzalez MC, Diaz P, Galleguillos FR, Ancic P, Cromwell O, Kay AB (1987) Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Am Rev Respir Dis 136: 600–604.PubMedGoogle Scholar
  30. 30.
    Broide DH, Firestein GS (1991) Endobronchial allergen challenge in asthma: demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization. J Clin Invest 88: 1048–1053.PubMedGoogle Scholar
  31. 31.
    Broide DH, Paine MM, Firestein GS (1992) Eosinophils express interleukin-5 and granulocyte macrophage colony-stimulating factor mRNA at sites of allergic inflammation in asthmatics J Clin Invest 90: 1414–1424.Google Scholar
  32. 32.
    Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR (1993) Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/ macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation in atopic asthmatics. Am J Respir Cell Mol Biol 8: 35–42.PubMedGoogle Scholar
  33. 33.
    Robinson DS (1993) Cytokines in asthma. Thorax 48: 845–853.PubMedGoogle Scholar
  34. 34.
    Schleimer RP, Sterbinsky SA, Kaiser J, et al. (1992) IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium: association with expression of VCAM-1. J Immunol 148: 1086–1092.PubMedGoogle Scholar
  35. 35.
    Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemokines: CXC and CC chemokines. Adv Immunol 55: 97–179.Google Scholar
  36. 36.
    Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301–314.PubMedGoogle Scholar
  37. 37.
    Baggiolini M, Dahinden CA (1994) CC chemokines in allergic inflammation. Immunol Today 15: 127–133.PubMedGoogle Scholar
  38. 38.
    Schall TJ, Bacon KB (1994) Chemokines, leukocyte trafficking, and inflammation. Cur Opin Immunol 6: 865–873.Google Scholar
  39. 39.
    Prieschl EE, Kulmburg PA, Baumruker T (1995) The nomenclature of chemokines. Int Arcl. Allergy Immunol 107: 475–483.Google Scholar
  40. 40.
    Alam R, Stafford S, Forsythe P, et al. (1993) RANTES is a chemotactic and activating factor for human eosinophils. J Immunol 150: 3442–3447.PubMedGoogle Scholar
  41. 41.
    Ebisawa N, Yamada T, Bickel C, Klunk D, Schleimer RP (1994) Eosinophilic transendothelial migration induced by cytokines: effect of the chemokine RANTES. J Immunol 153: 2153–2160.PubMedGoogle Scholar
  42. 42.
    Dahinden CA, Geiser T, Brunner T, et al. (1994) Monocyte chemotactic protein 3 is a most effective basophil-and eosinophil-activating cytokine. J Exp Med 179: 751–756.PubMedGoogle Scholar
  43. 43.
    Ying S, Taborda-Barata L, Meng Q, Humbert M, Kay AB (1995) The kinetics of allergen-induced transcription of messenger RNA for monocyte chemotactic protein-3 and RANTES in the skin of human atopic subjects: relationship to eosinophil, T-cell, and macrophage recruitment. J Exp Med 181: 2153–2159.Google Scholar
  44. 44.
    Schall TJ, Bacon K, Toy KJ, Goeddel TV (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347: 669–671.PubMedGoogle Scholar
  45. 45.
    Humbert M, Ying S, Corrigan C, et al. (1997) Bronchial mucosal gene expression of the CC chemokines RANTES and MCP-3 in symptomatic atopic and non-atopic asthmatics: relationship to the eosinophilactive cytokines IL-5, GM-CSF and IL-3. Am J Respir Cell Mol Biol 16: 1–8.PubMedGoogle Scholar
  46. 46.
    Kruisbeek AM (1993) Development of alpha beta T cells. Curr Opin Immunol 5: 227–234.PubMedGoogle Scholar
  47. 47.
    Leiden JM (1993) Transcriptional regulation of T cell receptor genes. Annu Rev Immunol 11: 539–570.PubMedGoogle Scholar
  48. 48.
    Spits H (1994) Early stages in human and mouse T cell development. Curr Opin Immunol 6: 212–221.PubMedGoogle Scholar
  49. 49.
    Augustin A, Kubo RT, Sim GK (1989) Resident pulmonary lymphocytes expressing the y/S T-cell receptor. Nature 340: 239–241.PubMedGoogle Scholar
  50. 50.
    Fajac I, Tazi A, Hance AJ, et al. (1992) Lymphocytes infiltrating normal human lung and lung carcinomas rarely express yS T cell antigen receptor. Clin Exp Immunol 87: 127–131.PubMedGoogle Scholar
  51. 51.
    Chan AC, Desai DM, Weiss A (1994) The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu Rev Immunol 12: 555–592.PubMedGoogle Scholar
  52. 52.
    McMenamin C, Pimm C, McKersey M, Holt PG (1994) Regulation of IgE responses to inhaled antigen in mice by antigen-specific yS T cells. Science 265: 1869–1871.PubMedGoogle Scholar
  53. 53.
    Okuda M, Pawankar R (1992) Flow cytometric analysis of intraepithelial lymphocytes in the human nasal mucosa. Allergy 47: 255–259.PubMedGoogle Scholar
  54. 54.
    Spinozzi F, Agea E, Bistoni O, et al. (1996) Increased allergen-specific, steroid sensitive yS T cells in bronchoalveolar lavage fluid from patients with asthma. Ann Int Med 124: 223–227.PubMedGoogle Scholar
  55. 55.
    Pawankar R, Okuda M, Asuma M, et al. (1995) Characterization of nasal yS T cells in perennial allergic rhinitis. J Allergy Clin Immunol 95: 190.Google Scholar
  56. 56.
    Rossman MD, Carding SR (1996) ’yy T cells in asthma. Ann Int Med 124: 266–267.Google Scholar
  57. 57.
    Marguerie C, Lunardi C, So A (1992) PCR-based analysis of the TCR repertoire in human autoimmune diseases. Immunol Today 13: 336–339.PubMedGoogle Scholar
  58. 58.
    Frew AJ, Dasmahapatra J (1995) T cell receptor genetics, autoimmunity and asthma. Thorax 10: 919–922.Google Scholar
  59. 59.
    Rackeman FM (1947) A working classification of asthma. Am J Med 3: 601–606.Google Scholar
  60. 60.
    Umibe T, Kita Y, Nakao A, et al. (1996) Analysis of T cell receptor clonotypes in bronchoalveolar lavage fluids of nonatopic asthmatics. J Allergy Clin Immunol 97: 309 (Abstract 505).Google Scholar
  61. 61.
    June CH, Bluestone JA, Nadler LM, Thompson CB (1994) The B7 and CD28 receptor families. Immunol Today 15: 321–331.PubMedGoogle Scholar
  62. 62.
    Thompson CB (1995) Distinct roles for the costimulatory ligands B7–1 and B7–2 in T helper cell differentiation? Cell 81: 979–982.PubMedGoogle Scholar
  63. 63.
    Freeman GJ, Boussiotis VA, Anumanthan A, et al. (1995) B7–1 and B7–2 do not deliver identical costimulatory signals, since B7–2 but not B7–1 preferentially costimulates the initial production of IL-4. Immunity 2: 523–532.PubMedGoogle Scholar
  64. 64.
    Ehlers S, Smith KA (1991) Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med 173: 25–36.PubMedGoogle Scholar
  65. 65.
    Lu P, Zhou XD, Chen SJ, et al. (1994) CTLA-4 ligands are required to induce an in vivo interleukin 4 response to a gastrointestinal nematode parasite. J Exp Med 180: 693–698.PubMedGoogle Scholar
  66. 66.
    Cony DB, Reiner SL, Linsley PS, Locksley RM (1994) Differential effects of blockade of CD28–B7 on the development of Thl or Th2 effector cell in experimental Leishmaniasis. J Immunol 153: 4142–4148.Google Scholar
  67. 67.
    Milich D, Linsley P, Hughes J, Jones J (1994) Soluble CTLA-4 can suppress autoantibody production and elicit long term responsiveness in a novel transgenic model. J Immunol 153: 429–435.PubMedGoogle Scholar
  68. 68.
    Bungre J, Till S, Larché M, et al. (1996) IL-5 secretion by allergen-specific CD4+ cells in short-term culture: dissociation from allergen-induced proliferation and dependence on B7–2 co-stimulation. J Allergy Clin Immunol 97: 359 (Abstract 708).Google Scholar
  69. 69.
    Till SJ, Larché M, Corrigan C, Dickason R, Huston D, Kay AB, Robinson DS. Dependence of allergen-induced T cell proliferation and cytokine production on CD28/CD86 costimulation. Clin Exp Immunol (submitted).Google Scholar
  70. 70.
    Del Prete GF, Maggi E, Parronchi P, et al. (1988) IL-4 is an essential co-factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants. J Immunol 140: 4193–4198.Google Scholar
  71. 71.
    Hirano T, Akira S, Taga T, Kishimoto T (1990) Biological and clinical aspects of interleukin-6. Immunol Today 443–449.Google Scholar
  72. 72.
    Zurawski G, de Vries JE (1994) Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 15: 19–26.PubMedGoogle Scholar
  73. 73.
    Humbert M, Grant JA, Taborda-Barata L, et al. (1996) High affinity IgE receptor ( FceRI)-bearing cells in bronchial biopsies from atopic and non-atopic asthma. Am J Respir Crit Care Med 153: 1931–1937.Google Scholar
  74. 74.
    Burrows B, Martinez FD, Halonen M, Barbee RA, Cline MG (1989) Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 320: 271–277.PubMedGoogle Scholar
  75. 75.
    Bentley AM, Menz G, Storz C, et al. (1992) Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa of intrinsic asthma: relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis 146: 500–506.PubMedGoogle Scholar
  76. 76.
    Humbert M, Durham SR, Ying S, et al. (1996) IL-4 and IL-5 mRNA and protein in bronchial biopsies from atopic and non-atopic asthmatics: evidence against “intrinsic” asthma being a distinct immunopathological entity. Am J Respir Crit Care Med 154: 1497–1504.PubMedGoogle Scholar
  77. 77.
    Walker C, Bode E, Boer L, Hansel TT, Blaser K, Virchow Jr J-C (1992) Allergic and non-allergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 146: 109–115.PubMedGoogle Scholar
  78. 78.
    Humbert M, Durham SR, Kimmitt P, et al. (1998) Elevated expression of mRNA encoding interleukin13 in the bronchial mucosa of atopic and non-atopic asthmatics. J Allergy Clin Immunol (in press).Google Scholar
  79. 79.
    Jabara HH, Fu SM, Geha RS, Vercelli D (1990) CD40 and IgE: synergism between anti-CD40 MAb and IL-4 in the induction of IgE synthesis by highly purified human B cells. J Exp Med 172: 1861–1864.PubMedGoogle Scholar
  80. 80.
    DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G (1993) CD40 ligand mutations in X-linked immunodeficiency with hyper IgM. Nature 361: 541–543.PubMedGoogle Scholar
  81. 81.
    EAACI (1993) Immunotherapy position paper. Allergy 48 (Suppl 14): 1–35.Google Scholar
  82. 82.
    BSACI Working Party (1993) Position paper on allergen immunotherapy. Clin Exp Allergy 23 (Suppl 3): 1–44.Google Scholar
  83. 83.
    Lichtenstein LM, Ishizaka K, Norman PS, Sobobka AK, Hill BM (1973) IgE antibody measurements in ragweed hayfever: relationship to clinical severity and the results of immunotherapy. J Clin Invest 52: 472–482.PubMedGoogle Scholar
  84. 84.
    Djurup R (1985) The subclass nature and clinical significance of the IgE antibody response in the patients undergoing allergen specific immunotherapy. Allergy 40: 469–486.PubMedGoogle Scholar
  85. 85.
    Creticos P, Franklin Adkinson N Jr, Kagey-Sobobka A, et al. (1985) Nasal challenge with ragweed in hayfever patients: effects of immunotherapy. J Clin Invest 76: 2247–2253.PubMedGoogle Scholar
  86. 86.
    Furin MJ, Norman PS, Creticos P, et al. (1991) Immunotherapy decreases antigen-induced eosinophil migration into the nasal cavity. J Allergy Clin Immunol 88: 27–32.PubMedGoogle Scholar
  87. 87.
    Otsuka H, Mezawa A, Ohnishi M, Okubo K, Seki H, Okuda M (1991) Changes in nasal metachromatic cells during allergen immunotherapy. Clin Exp Allergy 21: 115–119.PubMedGoogle Scholar
  88. 88.
    Rak S, Lowhagen O, Venge P (1988) The effect of immunotherapy on bronchial hyperresponsiveness and eosinophil cationic protein in pollen allergic patients. J Allergy Clin Immunol 82: 470–480.PubMedGoogle Scholar
  89. 89.
    Durham SR, Varney V, Gaga M, Trew AS, Jacobson M, Kay AB (1991) Immunotherapy and allergic inflammation. Clin Exp Allergy 21: 206–210.PubMedGoogle Scholar
  90. 90.
    Rocklin RE, Sheffer AL, Greineder DR, Melmon KL (1980) Generation of antigen-specific suppressor cells during allergy desensitization. N Engl J Med 302: 1213–1219.PubMedGoogle Scholar
  91. 91.
    Varney V, Gaga M, Frew AJ, Aber VA, Kay AB, Durham SR (1991) Usefulness of immunotherapy in patients with severe hayfever uncontrolled by antiallergic drugs. Br Med J 302: 265–269.Google Scholar
  92. 92.
    Varney VA, Hamid QA, Gaga M, et al. (1993) Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous response. J Clin Invest 92: 644–651.PubMedGoogle Scholar
  93. 93.
    Secrist H, Chelen CJ, Wen Y, Marshall JD, Umetsu DT (1993) Allergen immunotherapy decreases interleukin 4 production in CD4+T cells from allergic individuals. J Exp Med 178: 2123–2130.PubMedGoogle Scholar
  94. 94.
    Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Mutter VR (1995) Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-g secretion in specific allergen-stimulated T-cell cultures. J Immunol 154: 4187–4194.PubMedGoogle Scholar
  95. 95.
    Durham SR, Varney VA, Jacobson MR, Sudderick RM, Kay AB (1993) Effect of grass pollen immunotherapy on allergen-induced early and late nasal responses. J Allergy Clin Immunol 91: 290 (abstract).Google Scholar
  96. 96.
    Durham SR, Asoufi B, Corrigan C (1996) Patterns of response to corticosteroids. In: Szefler SJ, Leung DYM, eds. Severe Asthma: Pathogenesis and Clinical Management. Marcel Dekker, New York, pp. 243–253.Google Scholar
  97. 97.
    Leung DYM (1996) The glucocorticoid receptor as a target in the pathogenesis of steroid resistant asthma. In: Szefler SJ, Leung DYM, eds. Severe Asthma: Pathogenesis and Clinical Management. Marcel Dekker, New York, pp. 285–311.Google Scholar
  98. 98.
    Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13: 136–142.PubMedGoogle Scholar
  99. 99.
    Kita H, Ohnishi T, Okubo Y, Weiler D, Abrams JS, Gleich GJ (1991) Granulocyte/macrophage colony-stimulating factor and interleukin-3 release from peripheral blood eosinophils and neutrophils. J Exp Med 174: 745–8.PubMedGoogle Scholar
  100. 100.
    Meng Q, Ying S, Assoufi B, Moqbel R, Kay AB (1996) Effects of dexamethasone, cyclosporin A and rapamycin on eosinophil degranulation and survival. J Allergy Clin Immunol 97: 277 (Abstract 379).Google Scholar
  101. 101.
    Triggiani M, Cirillo R, Lichtenstein LM, Maroni G (1989) Inhibition of histamine and prostaglandin D2 release from human lung mast cells by cyclosporin A. Int Arch Allergy Appl Immunol 88: 253–255.PubMedGoogle Scholar
  102. 102.
    Casolaro C, Spadaro G, Patella V, Maroni G (1993) In vivo characterisation of the anti-inflammatory effect of cyclosporin A on human basophils. J Immunol 151: 5563–5573.PubMedGoogle Scholar
  103. 103.
    Hatfield SM, Roehm NW (1992) Cyclosporin and FK506 inhibition of murine mast cell cytokine production. J Pharm Exp Therap 260: 280–288.Google Scholar
  104. 104.
    Ellis CN, Fradin MS, Messana JM, et al. (1991) Cyclosporin for plaque-type psoriasis: results of a multidose, double-blind trial. N Engl J Med 324: 277–284.PubMedGoogle Scholar
  105. 105.
    Sowden JM, Berth-Jones J, Ross JS, et al. (1991) Double-blind, controlled, cross-over study of cyclosporin in adults with severe refractory atopic dermatitis. Lancet 338: 137–140.PubMedGoogle Scholar
  106. 106.
    Brynskov J, Freund L, Rasmussen SN, et al. (1989) A placebo-controlled, double-blind, randomised trial of cyclosporin therapy in active Crohn’s disease. N Engl J Med 321: 845–850.PubMedGoogle Scholar
  107. 107.
    Corrigan CJ, Brown PH, Barnes NC, Tsai J-J, Frew AJ, Kay AB (1991) Glucocorticoid resistance in chronic asthma: peripheral blood T lymphocyte activation and comparison of the T lymphocyte inhibitory effects of glucocorticoids and cyclosporin A. Am Rev Respir Dis 144: 1026–1032.PubMedGoogle Scholar
  108. 108.
    Alexander AG, Barnes NC, Kay AB (1992) Trial of cyclosporin on corticosteroid-dependent asthma. Lancet 339: 324–328.PubMedGoogle Scholar
  109. 109.
    Lock S, Kay AB, Barnes NC (1996) Double-blind, placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependent asthma. Am J Respir Crit Care Med 153: 509–514.PubMedGoogle Scholar
  110. 110.
    Nizankowska E, Soja J, Pinis G, et al. (1995) Treatment of steroid-dependent bronchial asthma with cyclosporin. Eur Respir J 8: 1091–1099.PubMedGoogle Scholar
  111. 111.
    Sihra B, Walker SM, Kon OM, Barnes NC, Kay AB (1996) Inhibition of the allergen-induced late phase asthmatic reaction by oral cyclosporin A. J Allergy Clin Immunol 97: 242 (Abstract 240).Google Scholar

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© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Marc Humbert
  • Stephen R. Durham

There are no affiliations available

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