title: Aire-dependent thymic development of tumor-associated regulatory T cells.
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.
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Malchow
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Leventhal
authors.forename: Saki
authors.initials: S
authors.lastname: Nishi
authors.forename: Benjamin I
authors.initials: BI
authors.lastname: Fischer
authors.forename: Lynn
authors.initials: L
authors.lastname: Shen
authors.forename: Gladell P
authors.initials: GP
authors.lastname: Paner
authors.forename: Ayelet S
authors.initials: AS
authors.lastname: Amit
authors.forename: Chulho
authors.initials: C
authors.lastname: Kang
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Geddes
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Peter A
authors.initials: PA
authors.lastname: Savage
mesh_terms: D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D001324:Autoantigens / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D018398:Homeodomain Proteins / Q000235:genetics; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011467:Prostate / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000096927:AIRE Protein
chemical_list: D000952:Antigens, Polyomavirus Transforming; D001324:Autoantigens; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D017430:Prostate-Specific Antigen; D014157:Transcription Factors; D000096927:AIRE Protein; C498833:Foxp3 protein, mouse; C064658:RAG-1 protein