Analysis of immunoregulatory pathways in murine pregnancy

Understanding how the antigenically foreign fetus escapes attack by maternal lymphoid cells has long been a goal of reproductive immunologists. The present thesis work analyzes the expression and regulation of maternal immunity to self Ia antigen, as well as to embryonic antigens common to fetal and tumor cells but absent from normal adult somatic tissues. Initial studies revealed that the in vitro proliferative capacity of thymus and bone marrow-derived T cells is enhanced during syngeneic murine pregnancy. Pregnancy was also found to promote the manifestation of autoreactive splenic T cells capable of mediating syngeneic graft-versus-host reactions. In addition, primigravid isopregnant mice harbour splenic T cells which are specifically sensitized to syngeneic fetal antigens. Both alpha-fetoprotein and a population of B-like pregnancy-associated splenic suppressor cells were shown to be potent regulators of autoimmune lymphoproliferative activity. Monoclonal antibodies (clone PSBA-1) were generated which, in the presence and absence of complement, abrogate the in vitro inhibitory activity of such suppressor cells. Moreover, a significant proportion of gravid females which were treated with PSBA-1 antibodies resorbed their embryos. Thus, a B-like suppressor cell appears to play a crucial immunoregulatory role during murine pregnancy