Pregnancy-induced T cell exhaustion: an opportunity to reduce immunosuppression

项目总结（摘要）

PROJECT SUMMARY (ABSTRACT) Pregnancy is a common alloimmunizing event that impacts transplant access and outcomes among women. Although T cells of the maternal immune system are routinely activated by fetal alloantigen, it is unclear whether T cells stimulated by fetal antigen differentiate into canonical memory cells during pregnancy. The long-term fate and recall potential of these antigen-experienced T cells in the maternal repertoire are of particular importance to female transplant recipients, whose T cells may be capable of rapid rejection of a donor organ that shares tissue antigens with a prior pregnancy. Unfortunately, our poor understanding of T cell fate in women with a history of pregnancy has contributed to significant gender disparity in transplantation. Preliminary data in our mouse model suggest that fetal antigen during pregnancy promotes the differentiation of CD8+ T cells that persist in the maternal repertoire but have restricted functionality. While these T cells can still mediate rapid allograft rejection, they appear to be distinct from memory T cells that differentiate during other types of alloimmunization. Different populations of antigen-experienced T cells in alloimmunized transplant recipients may have unique requirements for immunosuppression. In this proposal, we will investigate how populations of antigen-experienced T cells induced by either pregnancy or transplantation differ from one another (Aim 1) and determine whether these differences promote immunosuppression reduction strategies in women (Aim 2). We anticipate that the knowledge generated by these studies will alter current immunosuppression strategies to improve the care of alloimmunized transplant recipients.