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. However, 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 that the striking absence of MHC class I molecules on most placenta trophoblasts protects the fetus from maternal immune attack, by creating transgenic mice which express Ld in giant cell trophoblasts. Second, because Fas ligand (FasL) may contribute to immune privilege, we tested whether functional FasL expression by the fetus, or Fas expression by the mother, contributes to successful reproduction in a fully allogeneic 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 outcome. These results suggest that during healthy allogeneic pregnancy, down-regulation of MHC class I and expression of FasL on placenta are not critical events, and other factors must prevent a harmful maternal immune response.
Rogers
A M
AM
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, USA.
Boime
I
I
Connolly
J
J
Cook
J R
JR
Russell
J H
JH
D019264:Adoptive Transfer; D000818:Animals; D053222:Fas Ligand Protein; D005260:Female; D005333:Fetus / Q000276:immunology*; D006183:H-2 Antigens / Q000502:physiology*; D064532:Histocompatibility Antigen H-2D; D007108:Immune Tolerance; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D019076:Transgenes; D014327:Trophoblasts / Q000276:immunology*; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D008562:Membrane Glycoproteins; D019014:fas Receptor