Linked Life Data

10359126

Source:http://linkedlifedata.com/resource/pubmed/id/10359126

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-6-30
pubmed:abstractText
The guanine nucleotide-exchange factor Vav is a regulator of antigen-mediated cytoskeletal reorganization required for receptor clustering, proliferation and thymic selection. Moreover, Vav has been identified as a major substrate in the CD28 signal transduction pathway and overexpression of Vav enhances TCR-mediated IL-2 secretion in T cells. Here we show that CD3- plus CD28-mediated proliferation and IL-2 production were reduced in vav gene-deficient T cells. However, Vav had no apparent role in phorbol 12-myristate 13-acetate-plus CD28-mediated proliferation and IL-2 production, suggesting that Vav acts downstream of the TCR/CD3 complex. In vivo, Vav expression was crucial to generate primary vesicular stomatitis virus (VSV)-specific cytotoxic T cell responses. In contrast, vav-/- mice exhibited a reduced but significant footpad swelling after lymphocytic choriomeningitis virus (LCMV) infections and mounted a measurable primary cytotoxic T cell response to LCMV. Upon in vitro restimulation, cytotoxic T cell responses of both VSV- and LCMV-infected mice reached near normal levels. Our data provide the first genetic evidence that Vav is an important effector molecule that relays antigen receptor signaling to IL-2 production and activation of cytotoxic T cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1709-18
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
The oncogene product Vav is a crucial regulator of primary cytotoxic T cell responses but has no apparent role in CD28-mediated co-stimulation.
pubmed:affiliation
Amgen Institute, Department of Medical Biophysics and Immunology, University of Toronto, Ontario, Canada. Jpenning@amgen.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't