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Aire-Dependent Thymic Development of Tumor-Associated Regulatory T Cells

2013; American Association for the Advancement of Science; Volume: 339; Issue: 6124 Linguagem: Inglês

10.1126/science.1233913

1095-9203

Sven Malchow, Daniel S. Leventhal, Saki Nishi, Benjamin I. Fischer, Lynn Shen, Gladell P. Paner, Ayelet S. Amit, Chulho Kang, Jenna Geddes, James P. Allison, Nicholas D. Socci, Peter A. Savage,

Immune Cell Function and Interaction

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.