For the past several years, our research efforts have been devoted to the understanding of IgA induction and regulation. Our previous observations have indicated that oral immunization with thymic-dependent (TD) antigens induces unique subpopulations of T helper (Th) cells in gut-associated lymphoreticular tissue (GALT), which mainly support IgA antibody responses. These unique subpopulations of Th cells from murine Peyer's patch (PP) have been isolated, cloned and maintained in long term in vitro cultures. These PP Th cell clones primarily support IgA isotype responses and have been designated PP Th A clones. During the past two years, our laboratory has placed emphasis on the characterization at the cellular level of these helper T cell clones. Based on these studies, we will investigate the mechanisms involved in T cell regulation of IgA isotype responses in this proposal. Our approach can be divided into two major categories: 1) Production of IgA isotype-specific regulatory T cell hybridomas (e.g., Fc receptor for IgA (Fcalpha R) bearing T cells) and 2) Characterization and function of Fc alpha R bearing T cells and the released Fcalpha R for IgA responses. In order to accomplish these goals, T-T hybridomas will be developed from PP Th A cells and used to investigate the molecular aspects of IgA isotype-specific T helper cell function. Supernatants from T-T hybridoma cells will be tested for helper factor (e.g., secreted or released soluble FcR for IgA (sFcalpha R) or immunoglobulin binding factor for IgA (IBFalpha)) which supports in vitro IgA responses in purified B cell cultures. Furthermore, we will produce and characterize T suppressor cell clones and use these in studies to investigate the role of T suppressor cells in negative regulation of the IgA immune response. Since Fcalpha R bearing isotype-specific T cells may regulate IgA responses, the effect of IgA on T-B collaboration for IgA responses will be examined in this proposal. These studies will provide new evidence for the important role of IgA specific regulatory T cells for the IgA immune response.
