An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires

Chyi Song Hsieh, Ye Zheng, Yuqiong Liang, Jason D. Fontenot, Alexander Y. Rudensky

Research output: Contribution to journalArticlepeer-review

410 Scopus citations

Abstract

The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3+) CD4+ regulatory T cells (Treg cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic Treg cells in TCRβ-transgenic mice was diverse and was more similar to that of peripheral Treg cells than that of nonregulatory T cells, suggesting that thymic Treg cells make a substantial contribution to the peripheral Treg cell population. Activated T cells in Foxp3-deficient mice, which lack Treg cells, 'preferentially' used TCRs found in the TCR repertoire of Treg cells in Foxp3-sufficient TCRβ-transgenic mice, suggesting that these self-reactive TCRs contribute to the pathology of Foxp3-deficient mice. Our analyses suggest that Treg cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs.

Original languageEnglish
Pages (from-to)401-410
Number of pages10
JournalNature immunology
Volume7
Issue number4
DOIs
StatePublished - Apr 2006

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