title: Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease.
abstract: Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.
authors.affiliation: Department of Biology, University of California San Diego, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Nishibori
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Leon
authors.initials: L
authors.lastname: Su
authors.forename: Michael
authors.initials: M
authors.lastname: David
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004198:Disease Susceptibility; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators