Impairment of host-versus-graft reaction in pregnant mice. II. Selective suppression of cytotoxic T-cell generation correlates with soluble suppressor activity and with successful allogeneic pregnancy.

Abstract The fetus resulting from an allogeneic (interstrain) mating represents a type of graft that is not rejected by the mother. We have studied the lymph nodes draining the uterus (DLN) of C3H mice which had been mated to DBA/2 males. In order to determine the mechanism by which allogeneic pregnancy inhibits the generation of cytotoxic T cells (CTL) reactive with paternal H-2 antigens, we show that the frequency of precursor cells that develop into CTL in the DLN is not reduced, and thus pregnancy suppresses the development of CTL from their precursors. This suppression, which has been associated with mitomycin C-resistant suppressor cells in the DLN, tends to be anatomically localized to the DLN, acts without specificity for paternal H-2 antigens, and is associated with a soluble suppressive activity which does not pass through an ultrafiltration membrane (25,000-dalton cutoff). Although CTL generation was suppressed in the DLN, the antibody response to sheep erythrocyte antigens was not impaired. Allogeneically mated CBA strain mice which spontaneously resorbed their fetuses appeared to lack the suppression of CTL generation found in successful pregnancies. The presence of cell-associated suppressor activity in the DLN appears to correlate with the occurrence of successful allogeneic pregnancy in mice.