1. Aire-dependent thymic development of tumor-associated regulatory T cells.
- Author
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Malchow S, Leventhal DS, Nishi S, Fischer BI, Shen L, Paner GP, Amit AS, Kang C, Geddes JE, Allison JP, Socci ND, and Savage PA
- Subjects
- Animals, Antigens, Polyomavirus Transforming genetics, Autoantigens immunology, CD4 Antigens analysis, Female, Forkhead Transcription Factors analysis, Homeodomain Proteins genetics, Male, Mice, Mice, Transgenic, Prostate-Specific Antigen immunology, Transcription Factors genetics, AIRE Protein, Immune Tolerance, Prostate immunology, Prostatic Neoplasms immunology, T-Lymphocytes, Regulatory immunology, Thymus Gland growth & development, Thymus Gland immunology, Transcription Factors immunology
- Abstract
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.
- Published
- 2013
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