Pregnant mice are not primed but can be primed to fetal alloantigens.

Abstract

In this report we present evidence gathered from various stages of murine pregnancy that indicates that pregnant females have no demonstrable immune effector function directed against their semiallogeneic fetuses. Specifically, by using in vitro assays we found that cytotoxic lymphocytes were not present in pregnant mice, and pregnant mice challenged with radiolabeled paternal strain leukemia cells showed no evidence of immune elimination. Nonetheless, immunity measurable both in vitro and in vivo was readily induced by priming with the paternal strain cells. No harm to the fetus was observed in primed mothers. These results cast doubt on the relevance of mechanisms proposed that involve systemic active suppression during pregnancy. The results are compatible with the hypothesis that the placenta acts as a barrier, preventing fetal cells from priming the mother.Allogeneic pregnancy is a natural instance of successful transplantation across major histocompatibility barriers in adult animals. Many hypotheses have been proposed to explain this apparent exception to the "laws" of transplantation, but none has emerged that successfully accounts for all the experimental observations (1). In this paper we put forward an hypothesis based on the passenger lymphocyte theory (2), and present experimental evidence that is consistent with this interpretation. The hypothesis states that the placenta presents an impermeable barrier to relevant cellular traffic from fetus to mother and vice versa (3,4). By relevant cellular traffic we mean in the former instance fetal cells that can serve to stimulate an effective maternal rejection response, and in the latter instance stimulated maternal effector cells. The hypothesis is a variant of the idea that the fetus exists in an immunologically privileged site, and. predicts that maternal cells capable of effector immunity against the semiallogeneic fetus do not exist during pregnancy, but priming by paternal strain alloantigen will cause their appearance. Even if they are artificially stimulated, placental impermeability insures that they can do no harm to the fetus. Experiments, in which both in vitro and in vivo assays for immunity were used, were carried out on pregnant mice. The results conform to the predictions of the hypothesis, namely that maternal immune cells are not primed but can be primed by injected stimulator cells bearing paternal strain alloantigens. MATERIALS AND METHODSMice. Inbred C3H/HeJ and BALB/cCR mice were obtained from the breeding facility at the University of Alberta (Ellerslie, AB). Pregnancies were timed by checking for vaginal plugs, and the day the plug was found was labeled day 0.In Vitro Effector Cell Generation and Assay. The second method of generating cytotoxic T cells involved using a modified Marbrook polyacrylamide raft culture system (7). Optimal conditions were briefly as follows: 2 X 106 splenic or mesenteric lymphocytes were mixed with 16 X 106 lethally irradiated (1500 R) stimulator splenic lymphocytes and placed on polyacrylamide r...

Rôle du placenta dans le maintien de l'allogreffe fétale

“…Such a treatment is also able to restore normal placental weight in auto-immune MRL Chaouat, 1974;Bell et Billington, 1983 Sulila, 1985 ;Rodger, 1985 ;Mattson et Holmdal, 1987). On peut même générer in vivo des effecteurs cytotoxiques cellulaires maternels antipaternels sans compromettre une gestation (Mitchison, 1953;Lanman et al, 1982;Wegmann et al, 1979 ;Chaouat et Monnot, 1984).…”

Popular myths in reproductive immunology

“…The uterine decidua is not an immunologically privileged site; allografts are rejected promptly if the mother is alloimmunized, and allografts at nonuterine sites are recognized and rejected in unprimed females (reviewed in Clark, 1991). By contrast, pregnant mothers, whether human or murine, do not reject gestating semi-allogeneic or completely allogeneic (foreign) embryos, even if pre-immunized against the alloantigens of the father (Wegmann et al, 1979). Further, a pregnant female can make an immune response to the foreign MHC and minor non-MHC antigens of her fetus, but anti-MHC antibodies are not harmful, unlike antibodies to blood group antigens such as Rh, which can cross trophoblast and attach to the baby's Rh-positive erythrocytes, and sensitized maternal T cells do not cause pathological conditions either (Lissauer et al, 2012).…”

Immunoregulatory activity of supernatants from shortterm cultures of mouse decidual tissue

“…In normal murine pregnancy, anti-paternal specific cytotoxic cells are reported to be rare or absent (Smith, Burton, Barg & Mitchell, 1978;Wegmann, Waters, Drell & Carlson, 1979;Gottesman & Stutman, 1980) and anti-paternal humoral immune responses are restricted to a few inbred strains (Kaliss, 1973;Bell & Billington, 1980,1981. Non-specific inhibitory factors produced locally from decidual tissue could provide an explanation for such observations (see Billington & Bell, 1982).…”