Linked Life Data

16210655

Source:http://linkedlifedata.com/resource/pubmed/id/16210655

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-10-7
pubmed:abstractText
Vgamma9Vdelta2(+) cells represent the major population of gammadelta T cells in primate blood and react in an MHC-unrestricted fashion to a set of low m.w. nonpeptide phosphoantigens. Two types of structurally related agonists have been discovered so far: the natural phosphoantigens (hydroxydimethyl allyl-pyrophosphate or isopentenyl-pyrophosphate (IPP)) acting directly on Vgamma9Vdelta2(+) TCR and aminobisphosphonates, which block the mevalonate pathway in target cells, leading to accumulation of natural phosphoantigens that in turn activate Vgamma9Vdelta2(+) cells. We demonstrate in the cynomolgus monkey that Vgamma9Vdelta2 can be manipulated in vivo with bromohydrin pyrophosphate (BrHPP)/Phosphostim, a potent synthetic agonist for which the mechanism of action is similar to natural phosphoantigens. Although of very short half-life, injection of BrHPP leads to strong activation of Vgamma9Vdelta2, inducing production of a high level of Th1 cytokines. Combination of BrHPP with low-dose rhIL-2 induces specific amplification of effector-memory peripheral Vgamma9Vdelta2 in blood in a dose-dependant manner. This transient response returns to baseline within 10-15 days. Successive infusions of BrHPP and rhIL-2 induce less vigorous expansions, suggesting a progressive exhaustion of the response. As no toxicity is detected with or without IL-2, this scheme represents a promising immunotherapeutic strategy for induction of systemic Th1 cytokines and massive expansion of gammadelta T cell subset with antitumor and anti-infectious properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5471-80
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16210655-Animals, pubmed-meshheading:16210655-Antigens, pubmed-meshheading:16210655-Cell Proliferation, pubmed-meshheading:16210655-Cells, Cultured, pubmed-meshheading:16210655-Dose-Response Relationship, Immunologic, pubmed-meshheading:16210655-Female, pubmed-meshheading:16210655-Humans, pubmed-meshheading:16210655-Interferon-gamma, pubmed-meshheading:16210655-Interleukin-2, pubmed-meshheading:16210655-Macaca fascicularis, pubmed-meshheading:16210655-Male, pubmed-meshheading:16210655-Models, Immunological, pubmed-meshheading:16210655-Phosphoproteins, pubmed-meshheading:16210655-Receptors, Antigen, T-Cell, gamma-delta, pubmed-meshheading:16210655-Recombinant Proteins, pubmed-meshheading:16210655-T-Lymphocyte Subsets, pubmed-meshheading:16210655-Tumor Necrosis Factor-alpha
pubmed:year
2005
pubmed:articleTitle
In vivo immunomanipulation of V gamma 9V delta 2 T cells with a synthetic phosphoantigen in a preclinical nonhuman primate model.
pubmed:affiliation
Innate Pharma, Marseilles, France. sicard@innate-pharma.fr
pubmed:publicationType
Journal Article