title: Autoimmune regulator (AIRE)-deficient CD8+CD28low regulatory T lymphocytes fail to control experimental colitis.
abstract: Mutations in the gene encoding the transcription factor autoimmune regulator (AIRE) are responsible for autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome. AIRE directs expression of tissue-restricted antigens in the thymic medulla and in lymph node stromal cells and thereby substantially contributes to induction of immunological tolerance to self-antigens. Data from experimental mouse models showed that AIRE deficiency leads to impaired deletion of autospecific T-cell precursors. However, a potential role for AIRE in the function of regulatory T-cell populations, which are known to play a central role in prevention of immunopathology, has remained elusive. Regulatory T cells of CD8(+)CD28(low) phenotype efficiently control immune responses in experimental autoimmune and colitis models in mice. Here we show that CD8(+)CD28(low) regulatory T lymphocytes from AIRE-deficient mice are transcriptionally and phenotypically normal and exert efficient suppression of in vitro immune responses, but completely fail to prevent experimental colitis in vivo. Our data therefore demonstrate that AIRE plays an important role in the in vivo function of a naturally occurring regulatory T-cell population.
authors: Institut National de la Santé et de la Recherche Médicale, Toulouse, France.
authors: Céline
authors: C
authors: Pomié
authors: Rita
authors: R
authors: Vicente
authors: Yirajen
authors: Y
authors: Vuddamalay
authors: Brita Ardesjö
authors: BA
authors: Lundgren
authors: Mark
authors: M
authors: van der Hoek
authors: Geneviève
authors: G
authors: Enault
authors: Jérémy
authors: J
authors: Kagan
authors: Nicolas
authors: N
authors: Fazilleau
authors: Hamish S
authors: HS
authors: Scott
authors: Paola
authors: P
authors: Romagnoli
authors: Joost P M
authors: JP
authors: van Meerwijk
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017634:Self Tolerance; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000096927:AIRE Protein
chemical_list: D018106:CD28 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D000096927:AIRE Protein