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

DA Kahn, D Baltimore - Proceedings of the National …, 2010 - National Acad Sciences
DA Kahn, D Baltimore
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
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 (HY) in
proportion to the fetal antigen load. A portion of the maternal immune response to fetal …
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.
National Acad Sciences