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 TCR beta-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 TCR beta-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.