Antigen Specific T Cell-Mediated Suppression

Abstract

In nonresponder (NR) mice bearing the H-2^{p, q, s} haplotypes, in vivo priming with L-glutamic acid⁶⁰-L-alanine³⁰-L-tyrosine¹⁰ (GAT) leads to a predominant suppressor T cell (T_s) response. Cell-free extracts obtained by sonication of such GAT-T_s contain a material(s) (GAT-T_sE) that suppresses the GAT-specific plaque-forming cell (PFC) response to the immunogenic complex GAT-methylated bovine serum albumin (GAT-MBSA) in syngeneic or allogeneic NR strains. In contrast, GAT-T_sE fails to directly suppress the anti-GAT PFC response of various responder (R) strains. We have recently described experimental conditions that allow the in vitro generation of GAT-T_s by using R spleen cells. We now report that culture supernatants of such in vitro induced GAT-T_s, generated in the absence of appropriate macrophage antigen presentation, contain a T cell-derived suppressive material (GAT-T_sF) that 1) acts without apparent genetic restriction on the primary in vitro GAT PFC response of R and NR mice, 2) binds specifically to antigen (GAT), and 3) bears determinants coded for by the I-J subregion of the H-2 complex. In addition, coculture of R spleen cells with in vitro derived GAT-T_sF leads to the induction of new GAT-T_s (T_s2) able to suppress syngeneic primary GAT PFC responses in vitro. These observations provide insight into the means by which GAT-T_s regulate GAT responses in R mice, as well as raise questions concerning the relationship between GAT-T_sE and GAT-T_sF.