The Journal of Experimental Medicine
Torrey Pines Biolabs
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Published online 29 December 2003 doi:10.1084/jem.20020509
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 25-34
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Impaired Development of CD4+ CD25+ Regulatory T Cells in the Absence of STAT1 : Increased Susceptibility to Autoimmune Disease



Takeaki Nishibori, Yoshinari Tanabe, Leon Su and Michael David

Division of Biological Sciences and University of California San Diego Cancer Center, University of California San Diego, La Jolla, CA 92093

Address correspondence to Michael David, Department of Biology, University of California San Diego, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093. Phone: (858) 822-1108; Fax: (858) 822-1106; email: midavid{at}ucsd.edu

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.

Key Words: STAT1 • EAE • autoimmune disease • regulatory T cells

Abbreviations used in this paper: CFSE, carboxyfluorescein diacetate succinimidyl ester; CNS, central nervous system; EAE, experimental autoimmune encephalomyelitis; MBP, myelin basic protein; MS, multiple sclerosis; STAT1, signal transducer and activator of transcription 1; TDS, T cell–depleted spleen cells.

T. Nishibori and Y. Tanabe contributed equally to this work.


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