Antigen-specific suppressor T-cell activity in genetically restricted immune spleen cells.

Abstract

Virgin spleen cells develop comparable primary antibody responses in vitro to syngeneic or allogeneic macrophages (M.vphi.) bearing the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT), whereas immune spleen cells primed with syngeneic or allogeneic GAT-M.vphi. develop secondary responses preferentially when stimulated with GAT-M.vphi. syngeneic to the GAT-M.vphi. used for priming in vivo. These restrictions are mediated by products of the I-A subregion of the H-2 complex and are operative at the level of the GAT-M.vphi.-immune helper T[thymus derived]-cell interactions. To investigate why these immune spleen cells fail to develop a significant antibody response to GAT-M.vphi. other than those used for in vivo immunization and determine the mechanism by which the restriction is maintained, spleen cells from virgin and syngeneic or allogeneic GAT-M.vphi.-primed mice were co-cultured in the presence of GAT-M.vphi. of various haplotypes. Antibody responses to GAT developed only in the presence of GAT-M.vphi. syngeneic to the M.vphi. used for in vivo priming; responses in cultures with GAT-M.vphi. allogeneic to the priming M.vphi. whether these M.vphi. were syngeneic or allogeneic with respect to the responding spleen cells, were suppressed. The suppression was mediated by GAT-specific radiosensitive T cells. Thus, development of GAT-specific suppressor T cells appears to be a natural consequence of the immune response to GAT in responder and nonresponder mice. The implications of stimulation of genetically restricted immune helper T cells, and antigen-specific, but unrestricted, suppressor T cells after immunization with GAT-M.vphi. in vivo are discussed in the context of regulatory mechanisms in antibody responses.