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

Science. 2013 Mar 8;339(6124):1219-24. doi: 10.1126/science.1233913.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Autoantigens / immunology
  • CD4 Antigens / analysis
  • Female
  • Forkhead Transcription Factors / analysis
  • Homeodomain Proteins / genetics
  • Immune Tolerance*
  • Male
  • Mice
  • Mice, Transgenic
  • Prostate / immunology*
  • Prostate-Specific Antigen / immunology
  • Prostatic Neoplasms / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*

Substances

  • APECED protein
  • Antigens, Polyomavirus Transforming
  • Autoantigens
  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Homeodomain Proteins
  • Transcription Factors
  • RAG-1 protein
  • Prostate-Specific Antigen