Down-regulation of cytotoxic T lymphocyte generation by two distinct suppressor-cell systems

Two distinct suppressor systems have been described that are capable of down-regulating in vivo generation of cytotoxic T cells directed toward haptenaltered self-antigens. One system, induced by hapten, involves three T cells that others have shown to function sequentially to suppress DTH. The initiator of this cascade is a T cell that is readily induced in spleens of mice injected intravenously with syngenic membrane-coupled hapten. This Ts, when triggered by the same syngeneic membrane-coupled hapten that induced it, elaborates a factor. The other two Ts arise in lymph nodes and spleens of mice painted epidermally with hapten. One of the two Ts in this set is readily armed by the factor of the first Ts. The factor confers its specificity and genetic restriction upon the accepting Ts. The latter, when properly triggered, makes a factor that is taken up by its companion Ts, which actually suppresses by way of a nonspecific factor. Whereas this Ts cascade is operative at the efferent limb of DTH, it mediates suppression only at the afferent phase of the CTL response. A distinctly different suppressor system is induced by minor locus (Mls) antigen. When Mlsd lymphoid cells are injected intravenously into Mlsc-possessing mice, an Lyt-1+ T-suppressor cell is generated that can be found in the spleen as well as among peritoneal exudate cells. This Ts interacts with macrophages to accomplish nonspecific suppression of the CTL response that is detectable both in vivo as well as in vitro. A Ts soluble product has been found to be effective to suppress CTL generation in vitro only when macrophages are present in culture. The macrophage that accomplishes suppression is I-A-. Although the afferent limb of the CTL response is down-regulated by this suppressor system, our in vitro culturing system is so structured as to make the helper T cell inactive. Thus, the mechanism of suppression must be oriented to the other early participants in the response, namely, precursor CTL, helper and differentiation factors, and/or the antigen-presenting cell.