Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN

Immune tolerance during human pregnancy is maintained by a range of modifications to the local and systemic maternal immune system. Lymphoid infiltration is seen at the implantation site of the fetal-maternal interface, and decidual NK cells have been demonstrated to facilitate extravillous trophoblast invasion into maternal decidua during the first trimester, optimizing hemochorial placentation. However, although there is considerable T cell infiltration of the maternal decidua, the functional properties of this T cell response remain poorly defined. We investigated the specificity and regulation of CD4⁺ and CD8⁺ T cells obtained from human third trimester decidua and demonstrated that decidual CD4⁺ and CD8⁺ T cells exhibit a highly differentiated effector memory phenotype in comparison with peripheral blood and display increased production of IFN-γ and IL-4. Moreover, decidual T cells proliferated in response to fetal tissue, and depletion of T regulatory cells led to an increase in fetal-specific proliferation. HY-specific T cells were detectable in the decidua of women with male pregnancies and were shown to be highly differentiated. Transcriptional analysis of decidual T cells revealed a unique gene profile characterized by elevated expression of proteins associated with the response to IFN signaling. These data have considerable importance both for the study of healthy placentation and for the investigation of the potential importance of fetal-specific alloreactive immune responses within disorders of pregnancy.