Immunoregulatory pathways in adult responder mice. I. Induction of GAT-specific tolerance and suppressor T cells for cellular and humoral responses.

This report describes the alteration of helper-suppressor balances in an immune response (Ir) gene-controlled system by varying the route and form of antigen injection. Adult responder BALB/c mice develop Lyt 1+2-, T cells for delayed-type hypersensitivity (DTH), and T-cell proliferative (Tprlf) responses to subcutaneous injection of either poly(Glu60Ala30Tyr10) (GAT)-coupled syngeneic spleen cells (GAT-SP) or GAT emulsified in complete Freund's adjuvant. In contrast, intravenous injection of adult responders with GAT-SP results in specific unresponsiveness for DTH, Tprlf, interleukin-2, and plaque-forming cell (PFC) responses. This tolerance is mediated by both suppressor T cells (Ts) and a functional clonal inhibition. Lyt 1-2+ Ts suppress the induction (afferent limb) of GAT-specific DTH and PFC but not Tprlf responses. The reduced T-cell proliferation observed in GAT-tolerant mice is due to a non-transferable mechanism(s), possibly functional clonal inhibition. Our data are compatible with a multi-step pathway involving both proliferating and non-proliferating helper T (Th) cells. In addition, the fine specificity of tolerance induction for DTH and Tprlf responses was examined by using the related antigens poly(Glu60Ala40) (GA) and poly(Glu50Tyr50) (GT). Tolerance is exquisitely specific, as GA tolerizes responses to GA and GAT, whereas GT tolerizes GAT but not GA responses. Thus, both the route and form of antigen administration are important to the induction and regulation of immune response in Ir gene-controlled systems. Possible mechanisms governing the Th/Ts balance and the induction of GAT-specific tolerance and suppression for cellular and humoral responses in adult responders are discussed.