An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires.
The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3(+)) CD4(+) regulatory T cells (T(reg) cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic T(reg) cells in TCRbeta-transgenic mice was diverse and was more similar to that of peripheral T(reg) cells than that of nonregulatory T cells, suggesting that thymic T(reg) cells make a substantial contribution to the peripheral T(reg) cell population. Activated T cells in Foxp3-deficient mice, which lack T(reg) cells, 'preferentially' used TCRs found in the TCR repertoire of T(reg) cells in Foxp3-sufficient TCRbeta-transgenic mice, suggesting that these self-reactive TCRs contribute to the pathology of Foxp3-deficient mice. Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs.
Department of Medicine and Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA. chsieh@im.wustl.edu
Chyi-Song
CS
Hsieh
Ye
Y
Zheng
Yuqiong
Y
Liang
Jason D
JD
Fontenot
Alexander Y
AY
Rudensky
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D015723:Gene Library; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell