Immunologic Research

, 41:137

Negative regulators in homeostasis of naïve peripheral T cells

  • Jaime F. Modiano
  • Lisa D. S. Johnson
  • Donald Bellgrau
Article

DOI: 10.1007/s12026-008-8017-1

Cite this article as:
Modiano, J.F., Johnson, L.D.S. & Bellgrau, D. Immunol Res (2008) 41: 137. doi:10.1007/s12026-008-8017-1
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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.

Keywords

T cellsMHCSensitizationDesensitizationCell cycleNegative regulationTolerance

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Jaime F. Modiano
    • 1
    • 2
    • 3
    • 4
    • 5
  • Lisa D. S. Johnson
    • 5
  • Donald Bellgrau
    • 1
    • 2
  1. 1.Integrated Department of ImmunologyUniversity of Colorado DenverDenverUSA
  2. 2.University of Colorado Cancer CenterDenverUSA
  3. 3.Department of Veterinary Clinical SciencesUniversity of MinnesotaSt. PaulUSA
  4. 4.University of Minnesota Cancer CenterMinneapolisUSA
  5. 5.Graduate Program on Microbiology, Cancer Biology and ImmunologyUniversity of MinnesotaMinneapolisUSA