How the fetus and placenta escape rejection during pregnancy likely involves local immune regulation within the maternal decidua, the specialized stromal tissue that surrounds the implanted embryo. Surprisingly, virtually nothing is known about dendritic cells at the maternal/fetal interface, despite the critical importance of this cell type in monitoring peripheral tissue for foreign antigens and controlling subsequent immune responses. Here, we use TCR-transgenic T cell adoptive transfers and a model antigen transgenic system to test whether an antigen expressed exclusively by the fetus and placenta is indeed presented by dendritic cells within the draining lymph nodes of the uterus, and whether the T cell response is tolerogenic or immunogenic (Aim 1). We will then directly characterize the phenotype of decidual dendritic cells and ask whether these cells appropriately mature and emigrate from the uterus under inflammatory and homeostatic conditions (Aim 2). Third, we will characterize the differential recruitment of dendritic cells to the decidua versus the overlying myometrium, and determine the fate of newly recruited progenitor cells (Aim 3). Lastly, we will study how differential chemokine expression in the decidua and myometrium might locally regulate dendritic cell trafficking (Aim 4). An understanding of how dendritic cell behavior is specialized at the maternal/fetal interface might not only help explain how the fetus escapes rejection during pregnancy, a major unsolved question in contemporary immunology, but will likely shed light onto the local regulation of dendritic cell function in peripheral tissues elsewhere in the body. ? ?
