TY - JOUR TI - Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey AU - ElTanbouly, Mohamed A. AU - Noelle, Randolph J. T2 - Nature Reviews Immunology AB - Following their exit from the thymus, T cells are endowed with potent effector functions but must spare host tissue from harm. The fate of these cells is dictated by a series of checkpoints that regulate the quality and magnitude of T cell-mediated immunity, known as tolerance checkpoints. In this Perspective, we discuss the mediators and networks that control the six main peripheral tolerance checkpoints throughout the life of a T cell: quiescence, ignorance, anergy, exhaustion, senescence and death. At the naive T cell stage, two intrinsic checkpoints that actively maintain tolerance are quiescence and ignorance. In the presence of co-stimulation-deficient T cell activation, anergy is a dominant hallmark that mandates T cell unresponsiveness. When T cells are successfully stimulated and reach the effector stage, exhaustion and senescence can limit excessive inflammation and prevent immunopathology. At every stage of the T cell’s journey, cell death exists as a checkpoint to limit clonal expansion and to terminate unrestrained responses. Here, we compare and contrast the T cell tolerance checkpoints and discuss their specific roles, with the aim of providing an integrated view of T cell peripheral tolerance and fate regulation. DA - 2020/10/19/ PY - 2020 DO - 10.1038/s41577-020-00454-2 DP - www.nature.com SP - 1 EP - 11 LA - en SN - 1474-1741 ST - Rethinking peripheral T cell tolerance UR - https://www.nature.com/articles/s41577-020-00454-2 Y2 - 2020/10/20/00:02:05 ER -