Negative regulators in homeostasis of naïve peripheral T cells.

Immunologic Research
Jaime F ModianoDonald Bellgrau

Abstract

It is now apparent that naïve peripheral T cells are a dynamic population where active processes prevent inappropriate activation while supporting survival. The process of thymic education makes naïve peripheral T cells dependent on interactions with self-MHC for survival. However, as these signals can potentially result in inappropriate activation, various non-redundant, intrinsic negative regulatory molecules including Tob, Nfatc2, and Smad3 actively enforce T cell quiescence. Interactions among these pathways are only now coming to light and may include positive or negative crosstalk. In the case of positive crosstalk, self-MHC initiated signals and intrinsic negative regulatory factors may cooperate to dampen T cell activation and sustain peripheral tolerance in a binary fashion (on-off). In the case of negative crosstalk, self-MHC signals may promote survival through partial activation while intrinsic negative regulatory factors act as rheostats to restrain cell cycle entry and prevent T cells from crossing a threshold that would break tolerance.

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Citations

Apr 10, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Thomas F O'Brien, Xiao-Ping Zhong
Jun 5, 2008·Cancer Immunology, Immunotherapy : CII·Cristan M JubalaJaime F Modiano
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Dec 15, 2016·Frontiers in Immunology·Zheng XuNicole Suciu-Foca

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