Active suppression of host-vs-graft reaction in pregnant mice. III. Developmental kinetics, properties, and mechanism of induction of suppressor cells during first pregnancy.

The mammalian fetus bears a wide variety of antigens against which the maternal immune system can react, and in an allogeneic mating, carries paternal transplantation antigens that elicit both a humoral and a cellular response. Nevertheless, the “fetal allograft” is not usually rejected. One explanation of this paradox may be selective suppression of the generation of effectors of transplantation immunity by the maternal immune system. We have previously studied the lymph nodes draining the uterus (DLN) of C3H/HeJ (H-2k) female mice mated to allogeneic DBA/2 (H-2d) males and have shown a localized impairment of the generation of cytotoxic T lymphocytes (CTL) in vivo and in vitro by DLN cells against paternal H-2d alloantigens. Suppression was attributed to the action of a mitomycin C-resistant suppressor cell and to a nonspecific soluble suppressor factor that was absent from the DLN of allogeneically mated CBA/J (H-2k) that were resorbing their fetuses. We now report that suppression of CTL generation develops early in the DLN of C3H/HeJ mice after mating and peaks at the time of implantation (“grafting”). Suppression of CTL generation occurs in syngeneic matings and in animals rendered pseudopregnant by sterile matings. However, the concentration of the immunosuppressive gestational hormone, progesterone, in suppressive supernatants obtained from the lymphoid cells of allopregnant mice appears to be insufficient to account for suppression of CTL generation by a direct mechanism. Furthermore, a distinct suppressor cell population sedimenting at 3 mm/hr was isolated from which soluble suppressor activity could be obtained by culturing in vitro at 37°C. Suppressor cell activity was not sensitive to treatment with anti-T cell serum (rabbit anti-mouse brain serum) plus complement, suggesting the possibility that the nonspecific suppression of CTL generation in the DLN of allopregnant mice may be associated with a non-T suppressor cell.