Pregnancy-associated suppressor cells in mice: functional characteristics of CD3+4-8-45R+ T cells with natural suppressor activity.

Natural suppressor (NS) cells are MHC-unrestricted regulatory cells with non-specific inhibitory activity for immune responses. In adult mice, NS cells are characteristically found in bone marrow and in splenic tissue following total lymphoid irradiation and cyclophosphamide treatments. Recently, we have shown that the spleens of pregnant mice harbour a population of lymphocytes which resemble NS cells in terms of phenotype and inhibitory activity. In this study, we use positive and negative selection techniques to further characterize splenic pregnancy-associated NS (SPANS) cells as predominantly 'double negative' T cells (CD3+4-8-) bearing receptors for the lectins wheat germ agglutinin and soybean agglutinin, as well as expressing CD45R and the heat-stable J11d.2 antigen. Taken together, these findings lead us to conclude that SPANS cells belong to an immature T cell lineage. In keeping with their T cell phenotype, SPANS cells do not express the natural killer (NK) cell-specific markers NK2.1 and asialoGM1 and do not mediate lytic activity against NK-sensitive YAC-1 cells, although natural cytotoxic activity against WEHI-164 cells was found to co-purify with SPANS cells. Suppressive activity of SPANS cells in mixed lymphocyte reactions (MLR) is abolished by treatment with mitomycin C, suggesting that natural suppression in this system is a proliferation-dependent phenomenon. Preincubation of SPANS cells with conditioned medium from Con A-stimulated T cell cultures results in augmented NS activity, indicating that SPANS cells respond to T cell signals. Our data suggest that SPANS cells mediate suppression via the elaboration of a soluble suppressor factor since SPANS cells do not require cell-cell contact to mediate suppression and supernatants from short-term cultures of SPANS cell-enriched SBA+ pregnancy spleen cells inhibit MLR. We believe that SPANS cell may be important in regulating hematopoiesis and maternal anti-fetal immunity during murine pregnancy.