Lymphocytes in asthma.

Much attention has been paid in recent years to the nature of inflammatory cells which infiltrate the bronchial mucosa in patients with asthma (1). It is generally agreed that inflammation may be responsible, at least in part, for the central pathophysiological features of the disease, namely variable airways obstruction and non-specific bronchial hyperreactivity. Thus, a knowledge of the factors which initiate and propagate inflammation is fundamental to an understanding of pathogenesis. Lymphocytes and eosinophils are prominent amongst cells infiltrating the bronchi in autopsy studies of asthma deaths (2). T-lymphocytes have a central role to play in any inflammatory process. They are the only cells capable of initiating an inflammatory response by direct recognition of 'foreign' antigens through the T-cell receptor. There is now considerable evidence that specialized subsets of T-cells orchestrate eosinophil recruitment and activation. Secretory products from activated eosinophils are believed to be responsible for many, if not all, of the pathological features of asthma (3). A fundamental question is how eosinophils selectively accumulate and become activated in the bronchial mucosa. Considerable light has been shed on this problem as a result of the discovery and characterization of lymphokines. For example, CD4+ T-lymphocytes, after activation by antigen, secrete a number of these protein products which can attract and activate other leucocytes and, in turn, promote their growth and differentiation (4). In this sense, activated CD4+ T-ceils are inflammatory cells in their own right and not simply 'helper' cells for the production of antibody as their traditional label would suggest. Activated Tlymphocytes are a major source of the iymphokines granulocyte/macrophage colony stimulating factor (GM-CSF) and interleukin-5 (IL-5), both of which have pronounced effects on eosinophils including prolongation of survival, enhanced adherence and activation to the 'hypodense' phenotype (5-9). Enhanced eosinophil survival, locally in the mucosa, may be one mechanism whereby these cells accumulate. Many of the effects of IL-5 are selective and not observed with neutrophils. For example, IL-5 produces selective hyperadherence of eosinophils (but not neutrophils) to vascular endothelium (10). The fact that T-lymphocyte clones from subjects with hypereosinophilic syndrome elaborated eosinophil differentiation factors, supports the hypothesis that eosinophil numbers and function are directly regulated by T-lymphocyte products (11). Additional protein products with effects on eosinophil function elaborated by activated T-lymphocytes continue to be described (12). These observations point to clear mechanisms whereby activated CD4 + T-lymphocytes could initiate and propagate a selective eosinophiirich inflammatory response in the bronchial mucosa and thus bring about an exacerbation of asthma symptoms. In addition to these wide ranging effects on eosinophils, T-lymphocytes also have an important role to play in the regulation of IgE synthesis. The T-lymphocyte-derived lymphokines interleukin-4 and interferon-gamma exert opposing effects on IgE elaboration (13). The precise relationship between atopic disease, as defined by the presence of allergenspecific IgE, and asthma is not clear; in particular, it is not known whether 'atopic asthma' and 'non-atopic asthma' represent separate disease entities or whether the atopic diathesis serves simply to increase the severity of asthmatic symptoms owing to local mediator release in the bronchi on exposure to allergens. It is clear that clinical manifestations of atopy do not invariably include bronchial hyperreactivity. Nevertheless, there is no doubt that IgE-mediated reactions can exacerbate asthmatic symptoms in certain atopic individuals, and so to this extent, at least, the regulation of IgE production is of relevance to this discussion. In summary, there exists adequate and increasing evidence to support the suggestions that activated CD4+ T-lymphocytes have the capacity to orchestrate a selective accumulation and activation of eosinophils in the asthmatic bronchial mucosa and