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Proc Natl Acad Sci U S A. 2010 May 18;107(20):9299-304. doi: 10.1073/pnas.1003909107. Epub 2010 May 3.

Pregnancy induces a fetal antigen-specific maternal T regulatory cell response that contributes to tolerance.

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  • 1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1740, USA.


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.

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