Humoral and Cellular Regulation of Alloimmunity in Pregnancy

By using the cell-mediated lympholysis (CML) test, it was found that lymphoid cells from pregnant BALB/c females (gravid by C57BL/6 males) were not directly cytotoxic for 51Cr-labeled target cells posessing the same haplotype as the paternal parent. During various stages of gestation and degrees of parity, splenic lymphocytes from interstrain (BALB/c × C57BL/6) pregnant mice were equivalent to those from virgin BALB/c females in their in vitro proliferative responses to paternal strain cells (C57BL/6) in the one-way mixed lymphocyte reaction (MLR) and also in their ability to develop in vitro into cytotoxic effector cells toward paternal strain alloantigens. Suppressor activity on the part of splenocytes from pregnant mice could not be detected in the MLR and CML assay. Heat-inactivated serum from allogeneically pregnant BALB/c mice, when compared to serum from virgin or syngeneically pregnant females, regularly depressed both proliferative and effector phases of the MLR between related parental strain cells. The degree of inhibition was related to the final concentration of pregnant serum in culture with 1 to 3% serum producing greater than 75% inhibition. The inhibitory serum was not cytotoxic by using a sensitive 51Cr release assay, and the suppressive effect was associated with histocompatibility differences between the BALB/c and C57BL/6 mating combination. Thus although pregnancy across strong H-2 differences acts as a poor in vivo inducer of the effector component of cellular immunity, the in vitro proliferative functions of spleen cells from pregnant mice are intrinsically normal, but may be modulated by factors present in pregnancy serum.