Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
1995-3-29
|
| pubmed:abstractText |
The "outside-in" signals produced by the interaction of integrin molecules with the extracellular matrix (ECM) trigger a multitude of cellular events. The vitronectin receptor (VNR), an alpha v beta 3 heterodimer, functions as a costimulatory molecule for the activation of a subset of V gamma 1.1/C gamma 4-bearing gamma/delta T cells, which have been postulated to recognize a ubiquitous self-antigen. We addressed the question of whether stimulation of these T cells requires both engagement of the VNR by ECM proteins and engagement of the TCR by its Ag. We introduced into a TCR- but VNR+ mutant T cell hybridoma, TG40 (derived from 2B4), a chimeric molecule that contains the cytoplasmic tail of the TCR zeta-chain fused to the cytoplasmic and transmembrane region of either human CD8 or human CD25. The transfectants expressing the chimeric molecules secreted IL-2 constitutively when the VNR was engaged with a ligand, e.g., provided by ECM proteins present in FCS. This constitutive cytokine secretion could be blocked with mAb directed against the VNR, with or the peptide RGD, or by growth in serum-free medium. VNR-mediated cell activation also induced the phosphorylation of the zeta-chain. Signaling through the zeta-chain was required, as cells transfected with a chimera containing only a 22 amino-acid long, truncated zeta-chain did not secrete IL-2 constitutively. Thus, we demonstrated that the binding of the VNR to ECM protein in the presence of the zeta-chain is sufficient to induce cytokine secretion by T cells and does not require the recognition of an Ag by the TCR. Such integrin-mediated, Ag-independent activation of T cells may play a critical role in the potentiation of inflammatory responses.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoadhesin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Vitronectin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
154
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2104-11
|
| pubmed:dateRevised |
2004-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:7532660-Animals,
pubmed-meshheading:7532660-Antigens,
pubmed-meshheading:7532660-Cytokines,
pubmed-meshheading:7532660-Extracellular Matrix Proteins,
pubmed-meshheading:7532660-Humans,
pubmed-meshheading:7532660-Hybridomas,
pubmed-meshheading:7532660-Integrins,
pubmed-meshheading:7532660-Lymphocyte Activation,
pubmed-meshheading:7532660-Mice,
pubmed-meshheading:7532660-Models, Biological,
pubmed-meshheading:7532660-Phosphorylation,
pubmed-meshheading:7532660-Receptors, Antigen, T-Cell, gamma-delta,
pubmed-meshheading:7532660-Receptors, Cytoadhesin,
pubmed-meshheading:7532660-Receptors, Vitronectin,
pubmed-meshheading:7532660-Signal Transduction,
pubmed-meshheading:7532660-T-Lymphocyte Subsets,
pubmed-meshheading:7532660-T-Lymphocytes,
pubmed-meshheading:7532660-Transfection
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Antigen-independent, integrin-mediated T cell activation.
|
| pubmed:affiliation |
Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
|
| pubmed:publicationType |
Journal Article
|