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rdf:type | |
lifeskim:mentions | |
pubmed:dateCreated |
1997-4-4
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pubmed:abstractText |
In this review, a sequential multiple-step model for T-cell activation is proposed. In a series of in vitro studies, highly purified freshly isolated human peripheral blood T lymphocytes were stimulated through the CD28 receptor, with mAb or with natural ligands B7-1 or B7-2, along with TCR stimulation, in the absence of other costimulatory interactions. Ligation of the CD28 receptor, along with stimulation of the TCR, was found to up-regulate pleiotropic in vitro activities, including the secretion of both Th1 and Th2-type cytokines, B-cell help, and the development of cytotoxic activity. This costimulatory action involves CD4+ and CD8+ as well as naive and memory T-cell subsets. The expression of B7-1 and B7-2 on professional APC in situ in both normal and pathological tissues, and its up-regulation on monocytes by GM-CSF and IFN-gamma is consistent with this role. Additional studies have addressed the contribution of interactions between CD28 and B7-1 and B7-2 in T-cell activation initiated by normal un-engineered APC, such as stimulation with recall antigens and primary MLR. Blockade of the interaction between CD28 and B7-1/B7-2 under these conditions failed to completely inhibit T-cell responses or to induce anergy. Complete inhibition and anergy were, however, induced with a combination of CsA, targeting downstream TCR-triggered signalling, as well as anti-B7-1- and anti-B7-2-directed reagents. Interestingly, and in contrast to anti-LFA-1 mAb, the addition of anti-B7-1 or anti-B7-2 reagents could be delayed until at least 48 h after the initiation of T-cell stimulation, indicating a requirement for a late interaction between CD28 and its counter-receptors. Interactions between CD40L on activated T cells and CD40 on APC may serve to sustain, enhance or prolong the presentation of B7-1 or B7-2 on the APC, and thus to prevent anergy induction, or ineffective or abortive T-cell stimulation. Based on these data a sequential multiple-step T-cell activation model is proposed, and novel strategies for immuno-intervention can be designed.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD86,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0105-2896
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
153
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
47-83
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9010719-Antigens, CD,
pubmed-meshheading:9010719-Antigens, CD40,
pubmed-meshheading:9010719-Antigens, CD80,
pubmed-meshheading:9010719-Antigens, CD86,
pubmed-meshheading:9010719-Clonal Anergy,
pubmed-meshheading:9010719-Gene Expression Regulation,
pubmed-meshheading:9010719-Immunosuppressive Agents,
pubmed-meshheading:9010719-Lymphocyte Activation,
pubmed-meshheading:9010719-Membrane Glycoproteins,
pubmed-meshheading:9010719-Models, Immunological,
pubmed-meshheading:9010719-Signal Transduction,
pubmed-meshheading:9010719-T-Lymphocytes
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pubmed:year |
1996
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pubmed:articleTitle |
CD80, CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model.
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pubmed:affiliation |
Department of Pathophysiology, Catholic University of Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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