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

Abstract

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.