Specific maternal anti-fetal lymphoproliferative responses and their regulation by natural immunosuppressive factors

Maternal immune responses to autologous and/or oncodevelopmental antigenic determinants expressed on fetal tissues may constitute a potential hazard to fetal survival distinct from the well-studied maternal immune reactivity directed against paternally-derived fetal alloantigens. Splenic T cells with a helper phenotype (Lyt 1+2-) obtained from primiparous CBA/J mice pregnant by syngeneic matings were found to proliferate in response to co-culture with syngeneic Lyt 1-2- fetal thymus cells. In contrast, splenic T cells from virgin animals failed to react against fetal stimulator cells, suggesting that autosensitization to fetal gene products is a pregnancy-associated phenomena. Addition of anti-Ia alloantiserum at initiation of culture virtually abrogated the blastogenic response by maternal T cells, indicating that this is an Ia-dependent reaction. The addition of natural suppressor (NS) cells or alpha-fetoprotein (AFP), both of which are naturally occurring pregnancy-associated immunoregulatory factors, was found to markedly inhibit in-vitro maternal anti-fetal autoreactivity. NS cells and AFP may play an important role in maintaining homeostasis in the fetal-placental environment during murine pregnancy.