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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 |
2010-12-24
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pubmed:abstractText |
Human V?9V?2 T cells are potent anti-tumor lymphocytes that specifically respond to pyrophosphate (phospho-) antigens, which constitute the basis of current ?? T-cell-based immunotherapy strategies. Despite a clear involvement of the TCR, the costimulation requirements of V?9V?2 T cells remain ill-defined. Here, we show that the expression of the CD27 receptor by the vast majority of V?9V?2 peripheral blood lymphocytes endows them with enhanced proliferative capacity upon ligation by its unique ligand CD70, a tumor necrosis factor superfamily member expressed on lymphoma B-cells but also on TCR-activated ?? T cells. Moreover, V?9V?2 T-cell treatment with soluble recombinant CD70 induced calcium signals and increased transcription of anti-apoptotic Bcl2a1 and cell-cycle-promoting Cyclin D2 genes. We further demonstrate that the manipulation of CD70-CD27 interactions significantly impacted on V?9V?2 T-cell survival, proliferation and cytokine secretion, in both loss-of-function and gain-of-function experiments. Thus, CD27 coreceptor signals strongly promoted the expansion of Th1-biased, CD27(+) V?9V?2 peripheral blood lymphocytes in the context of TCR-mediated stimulation with phosphoantigens. These data collectively establish a novel role for the CD70-CD27 axis in human ?? T-cell activation and hence open new perspectives for its modulation in clinical settings.
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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/Antigens, CD27,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD70,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2-related protein A1,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
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 |
1521-4141
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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pubmed:issnType |
Electronic
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
195-201
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pubmed:meshHeading |
pubmed-meshheading:21182090-Antigens, CD27,
pubmed-meshheading:21182090-Antigens, CD70,
pubmed-meshheading:21182090-Calcium,
pubmed-meshheading:21182090-Cell Communication,
pubmed-meshheading:21182090-Cell Proliferation,
pubmed-meshheading:21182090-Cell Survival,
pubmed-meshheading:21182090-Cells, Cultured,
pubmed-meshheading:21182090-Cyclin D2,
pubmed-meshheading:21182090-Cytokines,
pubmed-meshheading:21182090-Humans,
pubmed-meshheading:21182090-Interleukin-2,
pubmed-meshheading:21182090-Lymphocyte Activation,
pubmed-meshheading:21182090-Organophosphorus Compounds,
pubmed-meshheading:21182090-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:21182090-Receptors, Antigen, T-Cell, gamma-delta,
pubmed-meshheading:21182090-T-Lymphocyte Subsets,
pubmed-meshheading:21182090-Th1 Cells,
pubmed-meshheading:21182090-Transcription, Genetic,
pubmed-meshheading:21182090-Tumor Necrosis Factor-alpha
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pubmed:year |
2011
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pubmed:articleTitle |
CD70-CD27 interactions provide survival and proliferative signals that regulate T cell receptor-driven activation of human ?? peripheral blood lymphocytes.
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pubmed:affiliation |
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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