Marilen Benner

CHAPTER 3 52 ABSTRACT During pregnancy, maternal regulatory T cells (Tregs) are important in establishing immune tolerance to invading fetal extravillous trophoblasts (EVTs). CD25 HI FOXP3+ Tregs are found at high levels in decidual tissues and have been shown to suppress fetus-specific and non- specific responses. However, limited data are available on additional decidual Treg types and the mechanisms by which they areinduced. This study investigated three distinct decidual CD4+ Treg types in healthy pregnancieswith a regulatory phenotype and the ability to suppress T cell responses: CD25 HI FOXP3+, PD1 HI IL-10+, and TIGIT+ FOXP3 dim . Moreover, co-culture ofHLA-G+ EVTs or decidual macrophages with bloodCD4+ T cells directly increased the proportions of CD25 HI FOXP3+ Tregs compared to T cells cultured alone. EVTs also increased PD1 HI Tregs that could be inhibited by HLA-C and CD3 antibodies, suggesting an antigen-specific induction. The presence of distinct Treg types may allowfor the modulation of a variety of inflammatory responses in the placenta.