A novel mechanism for the selection of isotype-specific antibody responses: the role of intestinal T cells in the regulation of IgA synthesis by the anti-suppressor circuit

Abstract

Within 6 hr of immunization the serum of mice contains a unique form of processed antigen, which consists of a complex of immunoglobulin (Ig) and antigen formed in the presence of a factor derived from the anti-suppressor inducer T cell. This complex binds to and activates the anti-suppressor effector T cell, which eventually leads to the inhibition of suppressor cell function. Both of these cells are present in the spleen (SPL) and play a role in the regulation of antibody responses. The purpose of these studies was to identify the anti-suppressor T cells in gut-associated lymphoid tissue and compare their function to their splenic counterparts. Inducer cells were detected in the Peyer's patches (PP), mesenteric lymph nodes but not in the intra-epithelial lymphocytes. The effector cells, which take up the complexes, were detected in PP and lamina propria lymphocytes but not in the intraepithelial or mesenteric lymph node lymphocytes. Furthermore, the uptake of the complexes correlated with the presence of T cells bearing Ia antigens. The PP and SPL anti-suppressor cells were compared for their ability to enhance the production of IgA and IgG. The data clearly showed that the product of the inducer cell, and the effector cell it activates, not only enhanced the antigen-specific responses but also selected for isotype-specific antibody responses. Cells from SPL enhanced IgG greater than IgA, whereas cells from PP selected for IgA. Thus, the presence in PP of cells in the anti-suppressor circuit and their ability to selectively promote IgA synthesis suggest that this regulatory mechanism plays a significant role in intestinal immune responses.