Costimulation through ICAM-1 induces the differentiation of human naïve CD4+ T cells to regulatory T cells: acquisition of distinct signaling and homing profiles during differentiation (89.39)

Abstract

Abstract Inducible regulatory T (Treg) cells are important mediators of peripheral tolerance that arise by mechanisms not fully defined. We have previously shown that a subset of human naïve CD4+ T cells that are costimulated through Intercellular Adhesion Molecule-1 (ICAM-1) will differentiate into cells with a Foxp3+CD25+CD127(-) phenotype and suppressive function characteristic of inducible Treg cells. Our present work identifies some of the signaling pathways that are activated during this differentiation process. We also characterize some of the chemokine receptors and other homing markers that are displayed on these Treg cells, including CCR7, CD62L, and specific integrins. These results help clarify the signaling requirements for in vitro differentiation of human naïve CD4+ T cells to Treg cells after costimulation through ICAM-1 and suggest possible microenvironments in which these cells could migrate and function during immune responses in vivo. This work was supported by the National Institute on Aging/NIH.