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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1999-3-5
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pubmed:abstractText |
In rheumatoid arthritis, T lymphocytes have been proposed to play a pivotal role in the disease process, but they have also been considered to simply represent an epiphenomenon in a primarily synoviocyte/macrophage-driven disease. To directly examine the contribution of CD4 T cells in synovitis, T cells were either depleted from or adoptively transferred into NOD-SCID mice engrafted with rheumatoid synovial tissue. Injection of anti-CD2 antibody resulted in the elimination of 80-90% of tissue-infiltrating T cells in the synovial grafts and was followed by a marked decline in the production of IL-1beta (loss of 70%), TNF-alpha (loss of 86%), and IL-15 (loss of 84%) mRNA. Also, transcription of MMP-1 and MMP-2 was reduced by 72% in anti-CD2-treated chimeras. Immunohistochemistry demonstrated that the cytokines and proteases derived mostly from CD68(+) synovial cells, which disappeared from the tissue upon T cell depletion. Adoptive transfer of autologous tissue-derived T cell lines and T cell clones into synovium-SCID mouse chimeras augmented the production of IFN-gamma as well as TNF-alpha in the synovial infiltrates. Administration of IFN-gamma in small doses to anti-CD2-treated chimeras restored the survival and the functional activity of CD68(+) synovial cells. In vitro studies confirmed the critical role of synovial T cells and IFN-gamma in the survival of synovial CD68(+) cells. These data demonstrate that the production of proinflammatory cytokines and of tissue-degrading enzymes in rheumatoid synovitis is T cell dependent and that CD4 T cells are primary regulatory cells in this disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD68 antigen, human,
http://linkedlifedata.com/resource/pubmed/chemical/Collagenases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1521-6616
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 1999 Academic Press.
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pubmed:issnType |
Print
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pubmed:volume |
90
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
65-78
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9884354-Adult,
pubmed-meshheading:9884354-Aged,
pubmed-meshheading:9884354-Aged, 80 and over,
pubmed-meshheading:9884354-Animals,
pubmed-meshheading:9884354-Antibodies,
pubmed-meshheading:9884354-Antigens, CD,
pubmed-meshheading:9884354-Antigens, Differentiation, Myelomonocytic,
pubmed-meshheading:9884354-Arthritis, Rheumatoid,
pubmed-meshheading:9884354-Cell Survival,
pubmed-meshheading:9884354-Collagenases,
pubmed-meshheading:9884354-Cytokines,
pubmed-meshheading:9884354-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9884354-Humans,
pubmed-meshheading:9884354-Immunotherapy, Adoptive,
pubmed-meshheading:9884354-Interferon-gamma,
pubmed-meshheading:9884354-Interleukin-1,
pubmed-meshheading:9884354-Interleukin-15,
pubmed-meshheading:9884354-Macrophages,
pubmed-meshheading:9884354-Matrix Metalloproteinase 1,
pubmed-meshheading:9884354-Matrix Metalloproteinase 3,
pubmed-meshheading:9884354-Mice,
pubmed-meshheading:9884354-Mice, Inbred NOD,
pubmed-meshheading:9884354-Mice, SCID,
pubmed-meshheading:9884354-Middle Aged,
pubmed-meshheading:9884354-Recombinant Proteins,
pubmed-meshheading:9884354-Synovitis,
pubmed-meshheading:9884354-T-Lymphocytes,
pubmed-meshheading:9884354-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Production of cytokines and metalloproteinases in rheumatoid synovitis is T cell dependent.
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pubmed:affiliation |
Division of Rheumatology, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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