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

被引:110
作者
Nishibori, T
Tanabe, Y
Su, L
David, M
机构
[1] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA
关键词
STAT1; EAE; autoimmune disease; regulatory T cells;
D O I
10.1084/jem.20020509
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Type I and 11 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.
引用
收藏
页码:25 / 34
页数:10
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  • [1] Barone C M, 1993, J Craniofac Surg, V4, P177, DOI 10.1097/00001665-199307000-00013
  • [2] Interferons α and β as immune regulators -: A new look
    Biron, CA
    [J]. IMMUNITY, 2001, 14 (06) : 661 - 664
  • [3] Failure to suppress the expansion of the activated CD4 T cell population in interferon γ-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis
    Chu, CQ
    Wittmer, S
    Dalton, DK
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (01) : 123 - 128
  • [4] Type IIFN modulates innate and specific antiviral immunity
    Durbin, JE
    Fernandez-Sesma, A
    Lee, CK
    Rao, TD
    Frey, AB
    Moran, TM
    Vukmanovic, S
    García-Sastre, A
    Levy, DE
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (08) : 4220 - 4228
  • [5] Targeted disruption of the mouse STAT1 results in compromised innate immunity to viral disease
    Durbin, JE
    Hackenmiller, R
    Simon, MC
    Levy, DE
    [J]. CELL, 1996, 84 (03) : 443 - 450
  • [6] TRANSGENIC MICE THAT EXPRESS A MYELIN BASIC PROTEIN-SPECIFIC T-CELL RECEPTOR DEVELOP SPONTANEOUS AUTOIMMUNITY
    GOVERMAN, J
    WOODS, A
    LARSON, L
    WEINER, LP
    HOOD, L
    ZALLER, DM
    [J]. CELL, 1993, 72 (04) : 551 - 560
  • [7] CD62L is required on effector cells for local interactions in the CNS to cause myelin damage in experimental allergic encephalomyelitis
    Grewal, IS
    Foellmer, HG
    Grewal, KD
    Wang, H
    Lee, WP
    Tumas, D
    Janeway, CA
    Flavell, RA
    [J]. IMMUNITY, 2001, 14 (03) : 291 - 302
  • [8] Interferon β in multiple sclerosis:: is IL-12 suppression the key?
    Karp, CL
    Biron, CA
    Irani, DN
    [J]. IMMUNOLOGY TODAY, 2000, 21 (01): : 24 - 28
  • [9] Defective TNF-alpha-induced apoptosis in STAT1-null cells due to low constitutive levels of caspases
    Kumar, A
    Commane, M
    Flickinger, TW
    Horvath, CM
    Stark, GR
    [J]. SCIENCE, 1997, 278 (5343) : 1630 - 1632
  • [10] An integrative model of regulation centered on recognition of TCR peptide/MHC complexes
    Kumar, V
    Sercarz, E
    [J]. IMMUNOLOGICAL REVIEWS, 2001, 182 : 113 - 121