Fetal expression of Fas ligand is necessary and sufficient for induction of CD8 T cell tolerance to the fetal antigen H-Y during pregnancy.
Interaction of Fas with Fas ligand (FasL) is known to play a role in peripheral tolerance mediated by clonal deletion of Ag-specific T cells. We have assessed the requirement for Fas/FasL interactions during induction of tolerance to the fetus. Using H-Y-specific TCR transgenic mice, we have previously demonstrated that exposure of maternal T cells to H-Y expressed by male fetuses results in deletion of 50% of H-Y-specific maternal T cells. The remaining H-Y-specific T cells were hyporesponsive to H-Y as assayed by decreased proliferative ability and CTL activity. To determine whether Fas/FasL interactions contribute to induction of maternal T cell tolerance, responsiveness to fetal H-Y was assessed in H-Y-specific TCR transgenic pregnant females that were deficient in functional Fas or FasL. Surprisingly, both deletion and nondeletion components of tolerance were abrogated in TCR transgenic H-Y-specific lpr (Fas-deficient) or gld (FasL-deficient) pregnant females. Experiments further revealed that expression of FasL by the fetus, but not by the mother, is necessary and sufficient for both components of maternal T cell tolerance to fetal Ags. Fas interaction with fetal FasL is thus critical for both deletion and hyporesponsiveness of H-Y-reactive CD8+ T cells during pregnancy.
Vacchio
Melanie S
MS
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA. vacchio@nih.gov
Hodes
Richard J
RJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D053222:Fas Ligand Protein; D005260:Female; D005333:Fetus / Q000276:immunology*; D006182:H-Y Antigen / Q000276:immunology*; D007108:Immune Tolerance; D008024:Ligands; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006182:H-Y Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor