J Exp Med. 2004 Jan 5; 199(1): 25-34
Nishibori T, Tanabe Y, Su L, David M.
Department of Biology, University of California San Diego, Bonner Hall
3138, 9500 Gilman Drive, La Jolla, CA 92093.
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.