T cells and chronic asthma.
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.
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Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
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D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens