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Immunol Res. 2008;41(2):137-53. doi: 10.1007/s12026-008-8017-1.

Negative regulators in homeostasis of naïve peripheral T cells.

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1
Integrated Department of Immunology, University of Colorado-Denver, Denver, CO, USA. modiano@umn.edu

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.

PMID:
18415030
PMCID:
PMC2587146
DOI:
10.1007/s12026-008-8017-1
[Indexed for MEDLINE]
Free PMC Article
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