Multiple mechanisms of peripheral T cell tolerance to the fetal "allograft".
The fetus represents a foreign entity to the maternal immune system, yet this "natural" allograft is not normally rejected. This unique situation provides a physiologic system to evaluate peripheral tolerance in which the maternal immune system is challenged with relatively rare Ags not previously encountered in the thymus. Using H-Y-specific TCR transgenic mice, we demonstrate that T cells specific for fetal Ags decrease in an Ag-specific manner during pregnancy and remain low postpartum, the result of an encounter with fetal cells expressing the appropriate MHC/peptide complexes. The finding that placental trophoblasts can induce Fas-mediated death of T cells is consistent with peripheral clonal deletion as one mechanism of tolerance. The remaining clonotypic T cells are unresponsive to antigenic stimulation, although neither TCR nor coreceptor is down-regulated. Our study demonstrates that specific recognition of fetal allogeneic Ags by maternal T cells results in tolerance induction of reactive T cells via multiple mechanisms.
Jiang
S P
SP
Laboratory of Immunology, Center for Biologics Evaluation Research and Review, U.S. Food and Drug Administration, Bethesda, MD, USA.
Vacchio
M S
MS
D000818:Animals; D017637:Clonal Deletion; D000939:Epitopes / Q000276:immunology; D005260:Female; D005333:Fetus / Q000276:immunology*; D007108:Immune Tolerance; D007519:Isoantigens / Q000276:immunology* / Q000502:physiology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
D000939:Epitopes; D007519:Isoantigens; D011948:Receptors, Antigen, T-Cell