Pregnancy-induced hyporesponsiveness to paternal alloantigens. II. Factors affecting altered expressions of immunity in parous rats.

It was previously demonstrated that female Fischer rats, primiparous by allogeneic DA males, produced only low levels of agglutinating antibody to a challenge skin graft bearing paternal alloantigens, although graft rejection was unimpaired. In this report, the phenomenon of pregnancy-induced hyporesponsiveness was further investigated with regard to factors responsible for its induction and maintenance. Increasing parity by DA males resulted in increased suppression of the Fischer females' agglutinating antibody production postpartum to a challenge skin graft bearing paternal antigens. Moreover, multiparity also resulted in impaired graft rejection, with greater numbers of litters causing more prolonged survival. Either humoral or cellular hyporesponsiveness, or both, persisted for several weeks or even months in many females. Removal of the iliac lymph nodes prior to pregnancy resulted in less severe suppression which was not maintained through the observation period (21 days postgrafting), whereas splenectomy either before mating or on day 7 of pregnancy had no effect. Tubal-ligated females exposed to multiple DA ejaculates, without pregnancy, manifested weakened humoral immunity similar to that of primiparous females, whereas those exposed to (Fischer X DA)F1 hybrid trophoblast multiple times in ectopic sites had not only somewhat suppressed antibody responses but also significantly impaired capacity to reject the challenge allograft. The potential roles of various antigenic stimuli and the complexities of intrauterine antigen processing during gestation are discussed in relation to this naturally induced allosuppression phenomenon.