Linked Life Data

18006849

Source:http://linkedlifedata.com/resource/pubmed/id/18006849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2007-11-16
pubmed:abstractText
In this study, the efficacy and mechanisms of chimeric NKG2D receptor (chNKG2D)-modified T cells in eliminating NKG2D ligand-positive RMA/Rae1 lymphoma cells were evaluated. Intravenous injection of RMA/Rae1 cells led to significant tumor formation in spleens and lymph nodes within 2 weeks. Adoptive transfer of chNKG2D-modified T cells after tumor injection significantly reduced tumor burdens in both spleens and lymph nodes, and prolonged the survival of tumor-bearing mice. Multiple treatments with chNKG2D T cells resulted in long-term tumor-free survival. Moreover, these long-term survivors were resistant to rechallenge with RMA tumor cells (NKG2D ligand-negative), and their spleen and lymph node cells produced IFN-gamma in response to RMA but not to other tumors in vitro, indicating immunity against RMA tumor antigens. ChNKG2D T cell-derived IFN-gamma and granulocyte-macrophage colony-stimulating factor, but not perforin (Pfp), tumor necrosis factor-related apoptosis-inducing ligand, or Fas ligand (FasL) alone were critical for in vivo efficacy. T cells deficient in both Pfp and FasL did not kill NKG2D ligand-positive RMA cells in vitro. Adoptive transfer of Pfp(-/-)FasL(-/-) chNKG2D T cells had reduced in vivo efficacy, indicating that chNKG2D T cells used both mechanisms to attack RMA/Rae1 cells. Taken together, these results indicate that chNKG2D T-cell-mediated therapeutic effects are mediated by both cytokine-dependent and cytotoxic mechanisms in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11029-36
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18006849-Animals, pubmed-meshheading:18006849-Cell Line, Tumor, pubmed-meshheading:18006849-Cell Proliferation, pubmed-meshheading:18006849-Cytokines, pubmed-meshheading:18006849-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:18006849-Humans, pubmed-meshheading:18006849-Interferon-gamma, pubmed-meshheading:18006849-Lymph Nodes, pubmed-meshheading:18006849-Lymphoma, T-Cell, pubmed-meshheading:18006849-Mice, pubmed-meshheading:18006849-Mice, Inbred C57BL, pubmed-meshheading:18006849-NK Cell Lectin-Like Receptor Subfamily K, pubmed-meshheading:18006849-Receptors, Immunologic, pubmed-meshheading:18006849-Receptors, Natural Killer Cell, pubmed-meshheading:18006849-Spleen, pubmed-meshheading:18006849-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:18006849-Treatment Outcome
pubmed:year
2007
pubmed:articleTitle
Chimeric NKG2D modified T cells inhibit systemic T-cell lymphoma growth in a manner involving multiple cytokines and cytotoxic pathways.
pubmed:affiliation
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural