Marilen Benner

CHAPTER 9 248 CHAPTER 3 | THREE TYPES OF FUNCTIONAL REGULATORY T CELLS CONTROL T CELL RESPONSES AT THE HUMAN MATERNAL- FETAL INTERFACE IFN ɣ dim CD25 PD1 IL-10 TIGIT+ FOXP3 FOXP3 Hi Hi Decidual Macrophages Extravillous Trophoblast MHC-II HLA-C IL-10 IFN ɣ TNFα IFN ɣ IL-10 Treg are induced by decidual macrophages and HLA-G+ EVT Three types of functional Treg are found at the maternal-fetal interface IL-10 IFN ɣ CD25 Hi PD1 Hi FOXP3 CD4+ CD8+ HELIOS HLA-G TCR • Three decidual Treg types suppress Teff responses in human pregnancy. • Decidual PD1 HI Tregs suppress T cell proliferation in an IL-10- dependent manner. • EVTs and decidual macrophages directly increase FOXP3+ Tregs, while EVTs also increase PD1 HI Tregs. • Induction of PD1 HI Tregs by EVTs may involve antigen-specificity for HLA-C.