Discrimination of 2 types of suppressor T cells by cell surface phenotype and by function: the ability to regulate the contrasuppressor circuit.

Contrasuppression is an immunoregulatory T cell activity that augments immune responses by interfering with suppressor T cell function. Since contrasuppression appears to play a role in autoimmunity, hyperimmunity, and recovery from induced general unresponsiveness (such as appears following burn trauma), an understanding of how contrasuppression is controlled may have profound implications for understanding immune regulation as well as for manipulating immune responses. Further, since inhibition of contrasuppressor function would appear as suppression, identifying cells able to perform this function would describe at least two modes of suppression in immune regulation, and allow a synthesis of regulatory T cell circuits not previously possible. In the studies described, we have sought to identify distinct lymphocyte subpopulation(s) having the specialized activity of regulating the cells of the contrasuppressor circuit. Two experimental systems have been previously examined. In the first, cells regulating the appearance of contrasuppressor effector T cells generated in cultures of neonatal spleen cells have been characterized. In the second, cells producing a contrasuppressor inducer factor derived from antigen-stimulated Ly-2 T cells have been studied, as well as their cellular targets. Regulation of contrasuppressor T cell activation in both systems by various cell populations was characterized by means of antisera against cell surface differentiation antigens. Our studies demonstrate that an I-J+, Ly-1,2 cell whose activity is not apparent before 1-2 weeks postbirth appears in adult T cell populations and regulates the generation of contrasuppressor cells in neonatal cell cultures. This adult cell can be removed with a low concentration of a monoclonal anti-T cell reagent. Removal of these T cells from adult populations allows the generation of an adult contrasuppressor effector cell indistinguishable from the one found in neonatal spleen by means of the spleen cell culture system. Adult antigen-primed Ly-2 T cells, used for the production of suppressor factor, contain a cell sensitive to the monoclonal antibody that normally prevents the dominance of contrasuppression over suppression. We refer to this cell as a "level 2" suppressor because after its removal contrasuppression is found, and after this contrasuppression is eliminated by selective antiserum treatment suppression is observed. This indicates that a "level 1" suppressor exists, but effector factors mediating this suppression are significantly more susceptible to contrasuppression than are those of "level 2" suppressor cells. Our findings demonstrate two types of suppressor cell circuits