Source:http://linkedlifedata.com/resource/pubmed/id/12707360
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2003-4-22
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pubmed:abstractText |
The etiology of autoimmune liver disease is poorly understood. BALB/c mice deficient in the immunoregulatory cytokine TGF-beta1 spontaneously develop necroinflammatory liver disease, but the immune basis for the development of this pathology has not been demonstrated. Here, we show that BALB/c-TGF-beta1(-/-) mice exhibit abnormal expansion in hepatic mononuclear cells (MNCs) compared with wild-type littermate control mice, particularly in the T cell and macrophage lineages. To test whether lymphocytes of the adaptive immune system are required for the spontaneous development of necroinflammatory liver disease, BALB/c-TGF-beta1(-/-) mice were rendered deficient in B and T cells by crossing them with BALB/c-recombinase-activating gene 1(-/-) mice. BALB/c-TGF-beta1(-/-)/recombinase-activating gene 1(-/-) double-knockout mice showed extended survival and did not develop necroinflammatory liver disease. The cytolytic activity of BALB/c-TGF-beta1(-/-) hepatic lymphocytes was assessed using an in vitro CTL assay. CTL activity was much higher in BALB/c-TGF-beta1(-/-) hepatic MNCs compared with littermate control hepatic MNCs and was particularly pronounced in the CD4(+) T cell subset. Experimental depletion of CD4(+) T cells in young BALB/c-TGF-beta1(-/-) mice prevented the subsequent development of necroinflammatory liver disease, indicating that CD4(+) T cells are essential for disease pathogenesis in vivo. These data definitively establish an immune-mediated etiology for necroinflammatory liver disease in BALB/c-TGF-beta1(-/-) mice and demonstrate the importance of CD4(+) T cells in disease pathogenesis in vivo. Furthermore, TGF-beta1 has a critical role in homeostatic regulation of the hepatic immune system, inhibiting the development or expansion of hepatic cytolytic CD4(+) T cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:CatesJustin M MJM,
pubmed-author:DuncanElizabeth MEM,
pubmed-author:DyerDarci ADA,
pubmed-author:FranzDouglas MDM,
pubmed-author:FrenchMargaret AMA,
pubmed-author:GorhamJames DJD,
pubmed-author:LinJack TJT,
pubmed-author:ParkIl-KyooIK,
pubmed-author:RudnerLynnie ALA,
pubmed-author:WhiteHillary DHD
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4785-92
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12707360-Animals,
pubmed-meshheading:12707360-Autoimmune Diseases,
pubmed-meshheading:12707360-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12707360-Crosses, Genetic,
pubmed-meshheading:12707360-Cytotoxicity, Immunologic,
pubmed-meshheading:12707360-Female,
pubmed-meshheading:12707360-Genetic Predisposition to Disease,
pubmed-meshheading:12707360-Hepatitis, Animal,
pubmed-meshheading:12707360-Immunity, Cellular,
pubmed-meshheading:12707360-Lymphocyte Depletion,
pubmed-meshheading:12707360-Male,
pubmed-meshheading:12707360-Mice,
pubmed-meshheading:12707360-Mice, Inbred BALB C,
pubmed-meshheading:12707360-Mice, Knockout,
pubmed-meshheading:12707360-Necrosis,
pubmed-meshheading:12707360-T-Lymphocyte Subsets,
pubmed-meshheading:12707360-Transforming Growth Factor beta,
pubmed-meshheading:12707360-Transforming Growth Factor beta1
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pubmed:year |
2003
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pubmed:articleTitle |
Necroinflammatory liver disease in BALB/c background, TGF-beta 1-deficient mice requires CD4+ T cells.
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pubmed:affiliation |
Department of Pathology, Dartmouth Medical School, Lebanon, NH 03756, 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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