The Evolving Role of T Cells in Allergic Disease
T Cells and Chronic AsthmaKon O.M. · Kay A.B.
Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London, UK
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There is increasing evidence that the asthma process is 'driven’ and maintained by persistence of a subset of chronically activated T memory cells, sensitized against allergenic, occupational or viral antigens which 'home’ to the lung after antigen exposure or viral infection. In general, allergens induce a CD4 T helper (Th) cell response, whereas viruses recognize CD8+ cytotoxic (Tc) T cells. In the asthmatic airways, there are CD4+ and, to a lesser number CD8+ cells with a type 2 cytokine phenotype (i.e., Th–2 and Tc–2 type). These cells produce interleukin (IL) 3 and 5 and granulocyte–macrophage colony–stimulating factor which recruit, mobilize and activate eosinophils for subsequent mucosal damage, as well as IL–4, an essential cofactor for local or generalized IgE production. This leads to epithelial shedding, mucus hypersecretion and bronchial muscle contraction. Thus, although the eosinophil may damage the mucosal surfaces in asthma, its function appears to be under T cell control. Support for this hypothesis includes: (1) activated T cells and their products can be identified in biopsies from the major variants of the disease (atopic, non–atopic and occupational asthma); (2) colocalization of mRNA for type 2 cytokines to CD4+ and CD8+ cells in atopic and non–atopic asthma; (3) the presence of activated cytokine–producing T cells in corticosteroid–resistant asthma; (4) the association of disease severity with type 2 cytokines, especially IL–5; and (5) the efficacy of cyclosporin A and a monoclonal anti–CD4 in chronic steroid–dependent disease. Inhibitors and/or antagonists directed against more precise T cell associated molecular targets hold promise for the future treatment of chronic asthma.
- Azzawi M, Bradley B, Jeffery PK, Frew AJ, Wardlaw AJ, Knowles G, Assoufi B, Collins JV, Durham S, Kay AB: Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthma. Am Rev Respir Dis 1990;142:1407–1413.
- Robinson DS, Bentley AM, Hartnell A, Kay AB, Durham SR: Activated memory T helper cells in bronchoalveolar lavage fluid from patients with atopic asthma: Relation to asthma symptoms, lung function, and bronchial responsiveness. Thorax 1993;48:26–32.
- Bentley AM, Maestrelli P, Saetta M, Fabbri LM, Robinson DS, Bradley BL, Jeffery PK, Durham SR, Kay AB: Activated T–lymphocytes and eosinophils in the bronchial mucosa in isocyanate–induced asthma. J Allergy Clin Immunol 1992;89:821–829.
- Bentley AM, Menz G, Storz C, Robinson DS, Bradley B, Jeffery PK, Durham SR, Kay AB: Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma: Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis 1992;146:500–506.
- Walker C, Bode E, Boer L, Hansel TT, Blaser K, Virchow JC Jr: Allergic and nonallergic asthmatics have distinct patterns of T–cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am Rev Respir Dis 1992;146:109–115.
- Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB: Predominant TH2–like bronchoalveolar T–lymphocyte population in atopic asthma. N Engl J Med 1992;326:298– 304.
- Ying S, Durham SR, Corrigan CJ, Hamid Q, Kay AB: 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 asthmatic and normal control subjects. Am J Respir Cell Mol Biol 1995;12:477–487.
- Ying S, Humbert M, Barkans J, Corrigan CJ, Pfister R, Menz G, Larche M, Robinson DS, Durham SR, Kay AB: Expression of IL–4 and IL–5 mRNA and protein product by CD4+ and CD8+ T cells, eosinophils, and mast cells in bronchial biopsies obtained from atopic and nonatopic (intrinsic) asthmatics. J Immunol 1997;158:3539–3544.
- Robinson DS, Ying S, Bentley AM, Meng Q, North J, Durham SR, Kay AB, Hamid Q: Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 1993;92:397– 403.
- Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR: Relationship between IL–4 and IL–5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 1997;156:704–708.
- Corrigan CJ, Brown PH, Barnes NC, Tsai JJ, Frew AJ, Kay AB: 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 1991; 144:1026–1032.
- Leung DY, Martin RJ, Szefler SJ, Sher ER, Ying S, Kay AB, Hamid Q: Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene expression in steroid–resistant asthma. J Exp Med 1995;181:33–40.
- Alexander AG, Barnes NC, Kay AB: Trial of cyclosporin in corticosteroid–dependent chronic severe asthma. Lancet 1992;339:324–328.
- Lock SH, Kay AB, Barnes NC: Double–blind, placebo–controlled study of cyclosporin A as a corticosteroid–sparing agent in corticosteroid–dependent asthma. Am J Respir Crit Care Med 1996;153:509–514.
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