Mechanisms of Regulation of Cell - Mediated

Thymus-derived suppressor cells (Ts)1 regulate humoral (1, 2), cell-mediated (3, 4), or proliferative (5) responses, and the characterization of these suppressor systems reveals that there are probably several distinct types of Ts. This has been further complicated by the demonstration in certain systems that one Ts or another immune cell may help induction of other phenotypically distinct Ts (6-10). These latter studies have raised the possibility that various Ts may in fact be part of a larger interrelated network of suppressor cells (11). Studies from this laboratory (7, 8, 10) designed to analyze the suppressor T cell network revealed that in several systems, antigen presented on syngeneic cells induces an antigen-specific I-J+ suppressor T cell, Tst, from which an antigen-specific, idiotype ÷, I-J+ suppressor factor, TsF1, can be obtained. TsFa, in turn, stimulates the development of a second set of suppressor T cells, Ts2, which are anti-idiotypic, I-J +, and which suppress antigen-specific immune cells. To better understand suppressor T cell networks we must determine what signals stimulate suppressor T cells. Compared with our detailed knowledge of the I regioncontrolled requirement for the stimulation of helper T cells by antigen, very little is known of the conditions for suppressor T cell stimulation. These experiments were designed to address this issue. We explored whether a major histocompatibility complex (MHC) requirement for the stimulation of suppressor T cells could be revealed by administering syngeneic spleen cells derivatized with a low density of hapten, a stimulus which is incapable of triggering suppression unless allogeneic cells are added, thus demonstrating the requirement of an allogeneic effect in the development of suppressor T cell responses. We then were able to verify that allogeneic T cells responding to I-J-coded differences on suppressor T ceils provided the necessary stimulus together with antigen, at the low dose used, for the development of specific suppression. The significance of this finding is discussed in relation to M H C restrictions in the development of suppressor T cell responses.