CD4+ CD25+ Foxp3+ T regulatory cells with limited TCR diversity in control of autoimmunity

Dennis Adeegbe, Takaji Matsutani, Jing Yang, Norman H. Altman, Thomas R. Malek

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The importance of high TCR diversity of Tregulatory (Treg) cells for self-tolerance is poorly understood. To address this issue, TCR diversity was measured for Treg cells after transfer into IL-2Rβ-/- mice, which develop lethal autoimmunity because of failed production of Treg cells. In this study, we show that high TCR diversity of pretransferred Treg cells led to selection of therapeutic Treg cells with lower TCR diversity that prevented autoimmunity. Pretransferred Treg cells with lower diversity led to selection of Treg cells through substantial peripheral reshaping with even more restricted TCR diversity that also suppressed autoimmune symptoms. Thus, in a setting of severe breakdown of immune tolerance because of failed production of Treg cells, control of autoimmunity is achieved by only a fraction of the Treg TCR repertoire, but the risk for disease increased. These data support a model in which high Treg TCR diversity is a mechanism to ensure establishing and maintaining self-tolerance.

Original languageEnglish (US)
Pages (from-to)56-66
Number of pages11
JournalJournal of Immunology
Volume184
Issue number1
DOIs
StatePublished - Jan 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> T regulatory cells with limited TCR diversity in control of autoimmunity'. Together they form a unique fingerprint.

  • Cite this