Source:http://linkedlifedata.com/resource/pubmed/id/12189525
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2002-8-21
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| pubmed:abstractText |
The herpes simplex virus thymidine kinase (HSV-tk) gene conferring ganciclovir (GCV)-specific sensitivity to transduced cells might control Graft-versus-Leukemia (GvL)/Graft-versus-Host Disease (GvHD). Human T lymphocytes were engineered with an LSN-tk retroviral vector encoding tk and neomycin resistance (NeoR) genes. A total of 80 x 10(6) tk(+) lymphocytes were injected intraperitoneally in NOD-SCID mice. Engraftment was evaluated by human CD45(+)/CD3(+) cytofluorimetric analysis and NeoR-based polymerase chain reaction (PCR) on peripheral blood, bone marrow, liver, thymus, and spleen on day +5. After 14 days, GCV (10 mg/kg daily) cytofluorimetric analysis and PCR were repeated (day +19). Immunohistological studies with anti-CD3 monoclonal antibody followed by alkaline phosphatase and monoclonal anti-alkaline phosphatase staining were performed on spleen and liver at the same time points. Human CD45(+)/CD3(+) cells were engrafted in all tissues on day +5 according to cytofluorimetry, immunohistology, and PCR. Lymphocytes "homed" to the white pulp T-cell area and to the red pulp; liver localization is prevalently at the periportal area. After GCV (day +19), cytofluorimetry and immunohistology showed very few CD3(+) cells. PCR identified the transgene in 22% tissue samples (positive only in thymus and spleen). GvHD did not occur in any animal. These data demonstrate elevated doses of human-transduced CD3(+) cells engraft in NOD/SCID mice; after GCV, very few CD3(+) cells can be detected and those that escape treatment can be found in the thymus and in the spleen on day +19. Lack of full response to GCV may account for cases of GvHD in patients receiving tk-transduced T lymphocytes.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
|
| pubmed:issn |
0929-1903
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| pubmed:author |
pubmed-author:AlfonsiDiegoD,
pubmed-author:BartoliAndreaA,
pubmed-author:BenedettiRobertaR,
pubmed-author:De IoanniMariangelaM,
pubmed-author:Di FlorioSabrinaS,
pubmed-author:Di IanniMauroM,
pubmed-author:FaliniBrunangeloB,
pubmed-author:FalzettiFrancaF,
pubmed-author:TabilioAntonioA,
pubmed-author:TerenziAdelmoA,
pubmed-author:VendittiGigliolaG
|
| pubmed:issnType |
Print
|
| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
756-61
|
| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12189525-Animals,
pubmed-meshheading:12189525-Antigens, CD,
pubmed-meshheading:12189525-Antiviral Agents,
pubmed-meshheading:12189525-Bone Marrow,
pubmed-meshheading:12189525-Cell Survival,
pubmed-meshheading:12189525-Cells, Cultured,
pubmed-meshheading:12189525-Flow Cytometry,
pubmed-meshheading:12189525-Ganciclovir,
pubmed-meshheading:12189525-Genetic Vectors,
pubmed-meshheading:12189525-Herpesviridae,
pubmed-meshheading:12189525-Humans,
pubmed-meshheading:12189525-Immunoenzyme Techniques,
pubmed-meshheading:12189525-Liver,
pubmed-meshheading:12189525-Lymphocyte Activation,
pubmed-meshheading:12189525-Lymphocyte Depletion,
pubmed-meshheading:12189525-Mice,
pubmed-meshheading:12189525-Mice, Inbred NOD,
pubmed-meshheading:12189525-Mice, SCID,
pubmed-meshheading:12189525-Moloney murine leukemia virus,
pubmed-meshheading:12189525-Polymerase Chain Reaction,
pubmed-meshheading:12189525-Spleen,
pubmed-meshheading:12189525-T-Lymphocytes,
pubmed-meshheading:12189525-Thymidine Kinase,
pubmed-meshheading:12189525-Thymus Gland,
pubmed-meshheading:12189525-Transduction, Genetic
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Homing and survival of thymidine kinase-transduced human T cells in NOD/SCID mice.
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| pubmed:affiliation |
Hematology and Clinical Immunology Section, Department of Clinical and Experimental Medicine, Perugia University, Perugia, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|