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

25 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 2008

Bibliographical note

Funding Information:
Acknowledgments The authors thank Dr. Stephen Jameson for his careful review of the manuscript and helpful suggestions. We regret if meritorious references may have been omitted in the interest of space or brevity. The work was supported by grants R21DK63410, P30CA46934, and R01DK58722 from the National Institutes of Health.


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


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