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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-7-23
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pubmed:abstractText |
CD28-B7 interaction plays a critical costimulatory role in inducing T cell activation, while CTLA-4-B7 interaction provides a negative signal that is essential in immune homeostasis. Transfer of CD45RB(high)CD4(+) T cells from syngeneic mice induces transmural colon inflammation in SCID recipients. This adoptive transfer model was used to investigate the contribution of B7-CD28/CTLA-4 interactions to the control of intestinal inflammation. CD45RB(high)CD4(+) cells from CD28(-/-) mice failed to induce mucosal inflammation in SCID recipients. Administration of anti-B7.1 (but not anti-B7.2) after transfer of wild-type CD45RB(high)CD4(+) cells also prevented wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of proinflammatory cytokines IL-2 and IFN-gamma by lamina propria CD4(+) cells. In contrast, anti-CTLA-4 treatment led to deterioration of disease, to more severe inflammation, and to enhanced production of proinflammatory cytokines. Of note, CD25(+)CD4(+) cells from CD28(-/-) mice similar to those from the wild-type mice were efficient to prevent intestinal mucosal inflammation induced by the wild-type CD45RB(high) cells. The inhibitory functions of these regulatory T cells were effectively blocked by anti-CTLA-4. These data show that the B7-CD28 costimulatory pathway is required for induction of effector T cells and for intestinal mucosal inflammation, while the regulatory T cells function in a CD28-independent way. CTLA-4 signaling plays a key role in maintaining mucosal lymphocyte tolerance, most likely by activating the regulatory T cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD86,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Cd86 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1830-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11466409-Adoptive Transfer,
pubmed-meshheading:11466409-Animals,
pubmed-meshheading:11466409-Antibodies, Monoclonal,
pubmed-meshheading:11466409-Antigens, CD,
pubmed-meshheading:11466409-Antigens, CD28,
pubmed-meshheading:11466409-Antigens, CD45,
pubmed-meshheading:11466409-Antigens, CD80,
pubmed-meshheading:11466409-Antigens, CD86,
pubmed-meshheading:11466409-Antigens, Differentiation,
pubmed-meshheading:11466409-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11466409-CTLA-4 Antigen,
pubmed-meshheading:11466409-Colitis,
pubmed-meshheading:11466409-Colon,
pubmed-meshheading:11466409-Cricetinae,
pubmed-meshheading:11466409-Female,
pubmed-meshheading:11466409-Immune Sera,
pubmed-meshheading:11466409-Immune Tolerance,
pubmed-meshheading:11466409-Immunoconjugates,
pubmed-meshheading:11466409-Injections, Intraperitoneal,
pubmed-meshheading:11466409-Intestinal Mucosa,
pubmed-meshheading:11466409-Membrane Glycoproteins,
pubmed-meshheading:11466409-Mice,
pubmed-meshheading:11466409-Mice, Inbred BALB C,
pubmed-meshheading:11466409-Mice, Knockout,
pubmed-meshheading:11466409-Mice, SCID,
pubmed-meshheading:11466409-Receptors, Interleukin-2,
pubmed-meshheading:11466409-T-Lymphocyte Subsets
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pubmed:year |
2001
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pubmed:articleTitle |
B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis.
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pubmed:affiliation |
Laboratory of Experimental Immunology, Department of Pathology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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