In vitro activity and in vivo correlates of alloantigen-specific murine suppressor T cells induced by allogeneic pregnancy.

The fetus that results from allogeneic mating in an outbred population bears a variety of antigens against which the maternal immune system reacts, but the type of immunity that is elicited by pregnancy does not mediate graft rejection. Previous studies have demonstrated the presence of nonspecific non-thymus derived suppressor cells in the lymph nodes draining the uterus (DLN) and in the uterine decidua during first allogeneic pregnancy. These suppressor cells appear to be small lymphoid cells that inhibit the generation of cytotoxic T cells (CTL) against paternal alloantigens. We now report that after a single allogeneic pregnancy, C3H and A strain mice develop paternal alloantigen-specific suppressor T cells (Thy-1.2+, Lyt-1-2+) that are distributed systemically in peripheral lymph nodes and spleen. These suppressor cells appear to act directly on CTL generation because the frequency of CTL precursors and the ability to produce T helper cells in response to paternal alloantigens remains unchanged after allogeneic pregnancy. Suppressor T cell activity could be detected both in vitro and in vivo, and the presence of suppression in vivo was associated with increased uterine weight 5 days after inoculation of allogeneic paternal tumor cells into the uterus of pseudopregnant mice. Nevertheless, both subcutaneous and intrauterine tumor inocula regressed in these mice with suppressor T cells. The possible role of suppressor T cells in contrast to non-T suppressor cells in successful reproduction and allopregnancy-induced tolerance is discussed.