Aire-dependent thymic development of tumor-associated regulatory T cells

Despite considerable interest in the modulation of tumor-associated Foxp3⁺ regulatory T cells (T_regs) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific T_regs (termed MJ23 T_regs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 T_regs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 T_regs underwent autoimmune regulator (Aire)-dependent thymic development in both male and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific T_regs, which are likely coopted by tumors developing within the associated organ.