CD4+CD25+ regulatory/suppressor T cells prevent allogeneic fetus rejection in mice

Recent evidences indicate that naturally occurring CD4+CD25+ regulatory/suppressor T cells (T(reg)) regulate not only autoimmunity, but also alloreactivity. In mice, they notably control tolerance to allogeneic transplants and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Here, we studied the role of T(reg) in maternal tolerance to fetuses, i.e. natural semi-allogeneic grafts. We show that semi-allogeneic pregnancies in mice induce an expansion of T(reg), but not of activated CD4+ and CD8+ T cells, in para-aortic lymph nodes draining fetal antigens. The treatment of female mice with an anti-CD25 antibody before mating results in depletion of T(reg) and expansion of activated CD4+ and CD8+ T cells solely in the draining lymph nodes, ultimately leading to fetus rejection. These observations were not made in the context of syngeneic pregnancies. Thus, T(reg) play a major role in maternal-fetal tolerance.