CCR7 coordinates paracrine interleukin-2 cross-talk between central memory and regulatory T cells and controls the homeostatic balance between regulatory T cell subsets (P1065)

Abstract

Abstract The importance of IL-2 in immune suppression mediated by Foxp3+ Treg cells is well established. However, IL-2 is not required for Treg cell development, in vitro suppression, or to maintain total cell number; thus, the mechanism by which IL-2 controls Treg cell activity remains unclear. We demonstrate that CD44lo CD62Lhi lymphoid tissue-resident Treg cells require IL-2 for survival and maintenance, whereas CD44hi CD62Llo Treg cells with a peripheral tissue homing phenotype are IL-2 independent. We termed these subsets central (cTr) and effector Treg (eTr) cells, respectively, due to their unique homeostatic requirements and migratory potential. Furthermore, we show that the chemokine receptor CCR7 provides cTr cells access to IL-2 by coordinating their localization in proximity to IL-2-producing CCR7+ Foxp3- central memory cells in the T cell zones of secondary lymphoid tissues. Collectively, our data demonstrate that the factors governing the homeostasis and maintenance of different Treg cell subsets are highly dependent on their tissue and microenvironment localization and indicate that loss of immune tolerance in the absence of IL-2 or CCR7 is due to an imbalance of cTr and eTr cells.