THE ROLE OF CD8(+) T-CELLS IN IMMUNOGLOBULIN-E REGULATION

The link between immunoglobulin E (IgE) antibodies and environmental allergens, allergic sensitization and atopic diseases such as asthma, rhinitis and eczema is well established, yet treatment of these diseases is largely symptomatic and fails to correct the underlying immune disorder. B-cell production of IgE depends on interleukin 4 (IL-4) and is inhibited by interferon (IFN-gamma). These cytokines are produced by T-helper 2 (Th2) and T-helper 1 (Th1) CD4(+) T cells respectively. In atopic dermatitis skin and asthmatic lung, Th2 cells predominate but antigen-specific CD4(+) T-cell clones derived from peripheral blood are a mixture of Th1, Th2, and Th0. Circulating allergen-specific CD4(+) T cells differentiate into Th1- and Th2-like clones in the presence of IL-12 and IL-4 respectively. In rats, CD8(+) T cells are potent regulators of IgE responses in vivo, although the mechanism for this is still unclear. CD8(+) T-cell depletion in immunized animals prolonged the IgE response but prior depletion did not. Indeed, prior depletion of CD8(+) T cells actually inhibited IgE production, suggesting that there may be more than one type of IgE regulatory CD8(+) T cell. This was supported by the observation that CD8(+) T cells inhibited the differentiation of both Th1 and Th2 CD4(+) T cells in vitro as well as IL-4- but not IL-2-induced Th2 CD4(+) T-cell growth. The existence of distinct CD8(+) T-cell subsets is supported by the observation that IL-4 and IFN-gamma regulate the growth and differentiation of CD8(+) T cells. IL-4 inhibits the development of CD8(+) T cells that produce IL-2 and IL-6 and enhances the generation of cells that make IL-4 and IL-5. A combination of IL-4 and anti-IFN-gamma enhanced IFN-gamma and IL-10 production. Studies are continuing to characterize different CD8(+) T-cell subsets at a clonal level and to determine their role in IgE regulation.