Regulation of costimulatory signal in maternal-fetal immune tolerance.

A pregnancy is associated with modifications in the immune status of the mother, but the mechanisms are not well understood. Several observations have indicated that CD28/CTLA-4 and B7-1/B7-2 are involved in the maternal-fetal immune regulation. This review aims to recapitulate our current knowledge concerning the role of CD28/CTLA-4 and B7-1/B7-2 in maternal-fetal immune regulation. Several studies suggest that up-regulation of B7-2 and/or CD28 and/or down-regulation of CTLA-4 are correlated with the occurrence of pregnancy loss. Therefore, an accurate expression of costimulatory molecules at the maternal-fetal interface may ensure that the decidual cells do not elicit a 'danger' signal to the maternal immune system, perhaps instead contributing to the establishment of immune tolerance in vivo. It is showed that costimulation blockade with anti-B7 mAbs results in altered allogeneic T-cell response and overcomes increased maternal rejection to the fetus, which improves fetus growth in the abortion-prone system. These findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells but also exert immunoregulatory effect on the maternal T cells. This procedure might be potentially useful to immunotherapy for human recurrent spontaneous abortion.