Nature Immunology 7, 401 - 410 (2006)
Published online: 12 March 2006; | doi:10.1038/ni1318
An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoiresChyi-Song Hsieh1, 3, Ye Zheng2, Yuqiong Liang2, Jason D Fontenot2
& Alexander Y Rudensky21
Department of Medicine and Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA. 2
Howard Hughes Medical Institute and Department of Immunology, University of Washington, Seattle, Washington 98195, USA. 3
Present address: Department of Medicine and Division of Rheumatology, Washington University, St. Louis, Missouri 63110, USA.
Correspondence should be addressed to Chyi-Song Hsieh chsieh@im.wustl.edu or Alexander Y Rudensky aruden@u.washington.edu 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 TCR -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 TCR-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.
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