The fetus and the maternal immune system: pregnancy as a model to study peripheral T-cell tolerance

In this article, we discuss recent findings that describe how maternal T cells respond upon encountering fetal antigens. Many earlier studies have characterized changes in the maternal T-cell repertoire of both humans and mice, yet it has been difficult to understand the significance of these findings since there has been no way to decipher if the alterations were the result of encounters with fetal antigens or were nonspecific changes related to pregnancy itself. Now, in the mouse, the availability of TCR transgenic mice and other technological advances allow direct visualization of the fate of maternal T cells that are reactive to the fetus and provide a means to probe the mechanisms by which tolerance to the fetus is maintained. This article focuses on how the fetus more closely resembles "developmental self' than a true allograft and how the study of maternal T-cell interactions with fetally derived antigens can be useful as a model for the study of peripheral T-cell tolerance.