Negative regulators in homeostasis of naïve peripheral T cells

Jaime F. Modiano, Lisa D S Johnson, Donald Bellgrau

Research output: Contribution to journalReview articlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)137-153
Number of pages17
JournalImmunologic Research
Issue number2
StatePublished - Jun 1 2008


  • Cell cycle
  • Desensitization
  • MHC
  • Negative regulation
  • Sensitization
  • T cells
  • Tolerance

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