FAS/FAS Ligand Interaction at the Placental Interface is not Required for the Success of Allogeneic Pregnancy in Anti-Paternal MHC Preimmunized Mice
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PROBLEM: FAS ligand (FASL) induces apoptosis in FAS+ T cells. FAS-FASL interaction can explain tolerance of some types of allografts. Do similar interactions prevent rejection of the fetal allograft and transplacental passage of maternal T cells capable of causing GvH leading to runting? METHOD OF STUDY: We examined growth of subcutaneous EL-4 (H-2b) tumor cells in syngeneic MRL.lpr/lpr mice mated with syngeneic MRL.lpr/lpr or allogeneic C57/B1/6.lpr/lpr males. Lpr/lpr mice lack FAS and their T cells should remain effective at the fetomaternal interface. In some studies, the mice were preimmunized against C57B1/6 to enhance the likelihood of fetal rejection and/or runting. Cytotoxic lymphocyte (CTL) activity in the spleens was assessed using a 51Cr-release assay. Birth weights and weights at weaning were measured. RESULTS: Tumor rejection was delayed by about 3 days in allopregnant lpr/lpr females compared to syngeneic pregnant females occurred, but tumors were rejected and in a secondary fashion with minimal delay allopregnant females preimmunized to H-2b. CTL activity was present more in decidua than in spleen in preimmunized mice, and allopregnancy failed to reduce this activity. No neonates born to preimmunized or control lpr/lpr mothers developed runt disease. Indeed, the birth weight was greater for immunized females, but at 10 weeks, the difference compared to non-immunized females disappeared. CONCLUSIONS: FAS/FASL interaction between FAS+ T cells and FASL+ fetal trophoblasts at the fetomaternal interface is not mandatory for successful allopregnancy. The potential roles of other apoptosis-induction mechanisms at the fetomaternal interface, such as TNF/TRAIL, require critical testing before enthusiasm is merited. It maybe necessary to eliminate all such mechanisms to show a deleterious effect on pregnancy. Spontaneous deletion of all pathways seems a priori unlikely to occur, and hence, of dubious relevance to fetal loss.
