Restricted Lymphokine Synthesis in CD4+ Helper T Cells: New Insights into the Regulation of IgE Synthesis and the Pathogenesis of Allergic Disease

Abstract

Over the past 5 years, a greater appreciation has developed regarding the role that IgE plays in the pathogenesis of allergic disease and asthma. Clinical investigators have shown that elevated IgE levels strongly correlate with the presence of asthma. In addition, other investigators have demonstrated that crosslinking of IgE on the surface of mast cells not only results in the release of histamine and other mediators but also produces a cascade of events leading to late phase reactions, bronchial hyperreactivity, and an allergic inflammatory response. Recent studies of the effects of a number of factors produced by CD4+ helper T lymphocytes—in particular, interleukin (IL) 4, IL-5 and IL-3—indicate that a distinct subtype of CD4+ T lymphocytes producing a specific profile of lymphokines greatly increases the secretion of IgE from B cells and enhances the accumulation of eosinophils and mast cells in the allergic inflammatory response. Thus, a complex network of cell types, including B cells producing IgE, mast cells, eosinophils, and subsets of CD4+ T lymphocytes secreting specific profiles of lymphokines, is involved in the development and regulation of allergic inflammation. This new understanding of allergic inflammatory disease and its dependence on IgE and on lymphokine synthesis in subsets of CD4+ T cells will lead to improved strategies in the treatment and control of allergic diseases.