Research Planning Grant: Studies of Maternal T-Cell Trafficking

Emory University, Atlanta GA

Investigators

Abstract

A fundamental unanswered question in cellular immunology is why the fetal-placental unit, a semi-allogeneic graft in direct contact with maternal tissue, is normally not rejected by the maternal immune system. Full investigation of this phenomenon promises to reveal basic methods by which the immune system, and by inference other complex biological systems, maintain homeostasis and meet complex and often competing requirements. That the mother does not reject the fetus because her immune system is physically limited or suppressed is a fundamental tenet of immunology. However, it is difficult to reconcile this long-held view with the fact that the fetus and the mother must be protected from infection. Moreover, there is evidence from studies of maternal immunity to the male H-Y antigen that refutes this concept. The H-Y antigen is expressed on male cells in all mammals as early as the blastocyst stage, and immunity can be easily generated in female mice by injection of male spleen cells. It has been found that maternal immunity to this antigen is not limited or suppressed by pregnancy. Yet, male fetuses are not rejected in immunized mothers. This project focuses on this apparent inconsistency through the use of transgenic mice and tetramer analysis to examine H-Y specific T-cells in immunized mothers. The overall hypothesis is that there may be unique patterns of fetal antigen-specific T-cell circulation in pregnanct mice. The work is likely to reveal novel mechanisms of immune cell homeostasis and circulation, and will further the understanding of molecular mechanisms of cellular trafficking to and across the maternal fetal interface. The project will also support the training of African American students, from high school to graduate and postdoctoral levels of training.