Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance.
A fetus is inherently antigenic to its mother and yet is not rejected. The T regulatory (Treg) subset of CD4(+) T cells can limit immune responses and has been implicated in maternal tolerance of the fetus. Using virgin inbred mice undergoing a first syngenic pregnancy, in which only the male fetuses are antigenic, we demonstrate a maternal splenocyte proliferative response to the CD4(+) T cell restricted epitope of the male antigen (H-Y) in proportion to the fetal antigen load. A portion of the maternal immune response to fetal antigens is Treg in nature. The bystander suppressive function of pregnancy-generated Tregs requires the presence of the fetal antigen, demonstrating their inherent antigen specificity. In vivo targeting of diphtheria toxin to kill Tregs leads to a lower fraction of live male offspring and a selective reduction in mass of the surviving males. Thus, Tregs generated in the context of pregnancy function in an antigen-specific manner to limit the maternal immune response to the fetus in a successful pregnancy.
Kahn
Daniel A
DA
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1740, USA.
Baltimore
David
D
D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005260:Female; D006182:H-Y Antigen / Q000276:immunology*; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D017931:DNA Primers; D000939:Epitopes; D006182:H-Y Antigen