MATERNAL-FETAL TOLERANCE IS MAINTAINED DESPITE TRANSGENE-DRIVEN TROPHOBLAST EXPRESSION OF MHC CLASS-I, AND DEFECTS IN FAS AND ITS LIGAND

During mammalian pregnancy, one or more semiallogeneic fetuses gestate in direct contact with the maternal circulation and uterine tissue. H owever, a damaging maternal immune response is not normally provoked. We studied two possible mechanisms for this maternal-fetal tolerance, alone and in combination. First, we directly tested the hypothesis tha t the striking absence of MHC class I molecules on most placenta troph oblasts protects the fetus from maternal immune attack, by creating tr ansgenic mice which express L-d in giant cell trophoblasts. Second, be cause Pas ligand (FasL) may contribute to immune privilege, we tested whether functional Fast expression by the fetus, or Pas expression by the mother, contributes to successful reproduction in a fully allogene ic breeding. Our data indicate that neither abnormal expression of MHC class I in giant cells, nor disruption of the Fas-FasL system, nor a combination of these two defects, has an adverse effect on pregnancy o utcome. These results suggest that during healthy allogeneic: pregnanc y, down-regulation of MHC class I and expression of Fast on placenta a re not critical events, and other factors must prevent a harmful mater nal immune response.