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
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.
Correspondence to: Dr. A.B. Kay
Allergy and Clinical Immunology, National Heart and Lung Institute
Imperial College School of Medicine,
Dovehouse Street, London, SW3 6LY (UK)
Tel. +44 171 376 3138, Fax +44 171 351 8181, E–Mail email@example.com
Number of Print Pages : 3
Number of Figures : 1, Number of Tables : 0, Number of References : 14
International Archives of Allergy and Immunology
Vol. 118, No. 2-4, Year 1999 (Cover Date: February-April 1999)
Journal Editor: D. Kraft, Vienna
ISSN: 1018–2438 (print), 1423–0097 (Online)
For additional information:http://www.karger.com/journals/iaa