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 TCRβ-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 TCRβ-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.