An antigen-specific signal is required for the activation of second-order suppressor T cells in the regulation of delayed-type hypersensitivity to 2,4,6-trinitrobenzene sulfonic acid.

Suppressor T cells (Ts-1) induced with trinitrophenyl (TNP)-conjugated syngeneic spleen cells (TNP-SC) can be enriched on antigen-coated plates and are afferent suppressors. In addition, these suppressor cells produced soluble suppressor factors (TsF) that were active in vivo. Therefore, the Ts-1 cells in the TNP system are very similar to the Ts-1 cells in other systems we have studied earlier. Further characterization of these TsF-1 revealed that TsF-1 obtained from TNP-SC-induced Ts-1 is major histocompatibility complex restricted in its activity. Injection of TNP-specific TsF-1 into naive mice did not induce Ts-2 unless additional corresponding antigen was provided. Moreover, the Ts-2 cells induced by administration of both TsF-1 and trinitrobenzene sulfonic acid were antigen specific rather than antiidiotypic.