Abstract

CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gene superfamily--is predominantly expressed on CD25(+)CD4(+) T cells and on CD25(+)CD4(+)CD8(-) thymocytes in normal naïve mice. We found that stimulation of GITR abrogated CD25(+)CD4(+) T cell-mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.

Keywords

IL-2 receptorTumor necrosis factor alphaBiologyImmunologyCytotoxic T cellCD8StimulationMonoclonal antibodyCell biologyT cellAntibodyImmune systemEndocrinologyIn vitroGenetics

MeSH Terms

AnimalsAutoimmune DiseasesCD4 AntigensCD4-Positive T-LymphocytesDimerizationGlucocorticoid-Induced TNFR-Related ProteinGlycoproteinsImmune ToleranceLymph NodesMiceMiceInbred BALB CRatsRatsWistarReceptorsInterleukin-2ReceptorsNerve Growth FactorReceptorsTumor Necrosis FactorSignal TransductionSpleenT-Lymphocyte Subsets

Affiliated Institutions

Related Publications

Blockade of Interleukin-6 Signaling Suppresses Not Only Th17 but Also Interphotoreceptor Retinoid Binding Protein–Specific Th1 by Promoting Regulatory T Cells in Experimental Autoimmune Uveoretinitis

Hiroshi Haruta , Nobuyuki Ohguro , Minoru Fujimoto +7 more

PURPOSE. Both Th17 and Th1 cells contribute to experimental autoimmune uveoretinitis (EAU). Interleukin-6 (IL-6) blockade inhibits Th17 differentiation in EAU and potently suppr...

2011 Investigative Ophthalmology & Visual ... 73 citations

Publication Info

Year
2002
Type
article
Volume
3
Issue
2
Pages
135-142
Citations
1710
Access
Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric
PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1710
OpenAlex
134
Influential
1359
CrossRef

Cite This

Jun Shimizu, Sayuri Yamazaki, Takeshi Takahashi et al. (2002). Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature Immunology , 3 (2) , 135-142. https://doi.org/10.1038/ni759

Identifiers

DOI
10.1038/ni759
PMID
11812990

Data Quality

Data completeness: 86%