T cell regulation of B cell activation. I-A-restricted T suppressor cells inhibit the major histocompatibility complex-restricted interactions of T helper cells with B cells and accessory cells

The present studies were carried out to characterize the cellular interactions involved in the activation and function of the antigen-specific and antigen-nonspecific T suppressor (Ts) cells that regulate the IgG responses of Lyb-5-B cells. The in vitro activation of both Lyt-1+2- antigen-nonspecific Ts cells and Lyt-1-2+ antigen-specific Ts cells was shown to require the interaction of accessory cells and antigen-primed T cells. It was further demonstrated that this interaction was major histocompatibility complex (MHC)-restricted in that T cell recognition of I-A-encoded determinants on accessory cells was required for Ts cell activation. The activation of antigen-primed (A X B)F1 T cells with antigen in the presence of parentA or parentB accessory cells resulted, respectively, in the generation of parentA-restricted or parentB-restricted Ts cells. ParentA-restricted F1 Ts cells suppressed the responses generated by (A X B)F1 T helper (Th) cells cooperating with parentA (B + accessory) cells but did not suppress responses by the same (A X B)F1 Th cell population cooperating with parentB (B + accessory) cells. Neither parentA-restricted Ts cells alone nor parentB-restricted Ts cells alone suppressed the responses of (A X B)F1 (B + accessory) cells, whereas a mixture of these two Ts cell populations was able to significantly suppress the responses of F1 (B + accessory) cells. In contrast, responses of (A X B)F1 leads to parentA Th cells (restricted to recognizing parentA but not parentB MHC determinants on F1 cells) and (A X B)F1 (B + accessory) cells was suppressed by parentA-restricted Ts cells but not by parentB-restricted Ts cells. Collectively these findings suggest that the Ts cell populations characterized here do not function by directly inhibiting the activity of Th cells, B cells or accessory cells of a given MHC genotype, but rather that they appear to function through a unique mechanism involving highly specific inhibition of the interaction between MHC-restricted Th cells and the (B + accessory) cells required for these responses.