AIRE-dependent T_Reg cells in tumours

Malchow et al. report a central role for the autoimmune regulator (AIRE)-dependent thymic expression of self antigens in the development of natural regulatory T (T_Reg) cells, and they indicate that natural T_Reg cells are the most prevalent type of T_Reg cells in at least some tumours. T cell receptor (TCR) repertoire analysis of T_Reg cells from autochthonous prostate tumours of transgenic mice identified selective enrichment of a T_Reg cell clone (referred to as an MJ23 T_Reg cell clone), which expressed a characteristic Vα2 TCRα chain that was absent in non-T_Reg cell TCRs. Next, studies in male and female transgenic mice, in which all T cells expressed the MJ23 TCR, showed that this TCR was specific for a prostate self antigen. MJ23 T_Reg cells did not differentiate from naive T cells intratumourally but developed in the thymus of both male and female mice in an AIRE-dependent manner. So, besides its central role in negative thymic selection, AIRE is involved in natural T_Reg cell development. The authors suggest that it is such self antigen-specific natural T_Reg cells (rather than tumour antigen-specific induced T_Reg cells) that accumulate in tumours.