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PMID: 14699080 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease.

The Journal of experimental medicine ·Vol. 199 ·No. 1 ·2004-01-05 ·Pages 25-34

Nishibori T, Tanabe Y, Su L, David M

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.

MeSH Terms
Adoptive Transfer Animals Autoimmune Diseases/genetics CD4-Positive T-Lymphocytes/immunology DNA-Binding Proteins/deficiency,genetics,physiology Disease Susceptibility Mice Mice, Knockout Mice, Transgenic Receptors, Antigen, T-Cell/genetics,immunology Receptors, Interleukin-2/immunology STAT1 Transcription Factor Signal Transduction T-Lymphocytes/immunology Trans-Activators/deficiency,genetics,physiology
Chemicals
DNA-Binding Proteins Receptors, Antigen, T-Cell Receptors, Interleukin-2 STAT1 Transcription Factor Stat1 protein, mouse Trans-Activators
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nishibori Takeaki
Department of Biology, University of California San Diego, Bonner Hall 3138, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Tanabe Yoshinari
Su Leon
David Michael
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20020509
Published
2004-01-05
Epub
2003-00-29
Pages
25-34
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC1193645
Subset
IM
Grants
NCI NIH HHS · R01 CA080105 · United States
NCI NIH HHS · CA 80105 · United States
External Links
PubMed source DOI: 10.1084/jem.20020509 PMC Full Text View journal details
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