1116 Cloned Helper T Cells for Immunoglobulin a Responses

The immunoglobulin A (IgA) response is thymic dependent (TD), 1 because athymic, nude mice exhibit depressed serum IgA levels (1-3) and neonatally thymectomized rabbits do not undergo IgA responses (4). Furthermore, human T cell dysfunctions contribute to IgA deficiency in some individuals (5-7). However, it has been difficult to directly study T cell regulation of IgA responses to specific antigens. Part of this difficulty has been because of nonuniform methods for isolation of T cells from inductive sites and to low frequencies of antigen-specific T helper (Th) cells in the T lymphocyte population. A major source of precursor cells for IgA responses is the gut-associated lymphoreticular tissue (GALT), e.g., Peyer's patches (PP), which contain antigen-sensitive T and B cells (8, 9) and accessory cells (M~0) (9-11). Oral immunization of mice with T D antigen sensitizes both T cells (12, 13) and precursor IgA B cells (14) in GALT. These sensitized cells leave the PP via efferent lymphatics and migrate to distant mucosal sites, where final differentiation of IgA precursor B cells leads to IgA expression. Elson and co-workers (15) reported that murine PP T cells, stimulated with concanavalin A (Con A), suppressed IgM and IgG and helped IgA isotype expression in LPS-driven B cell cultures, whereas Con A-treated splenic T cells suppressed all three isotypes. Our previous studies (13) have shown that gastric intubation of sheep erythrocytes (SRBC) induces significant Th cell activity in the murine PP. Furthermore, in vitro immunization with SRBC of PP cells from orally