Source:http://linkedlifedata.com/resource/pubmed/id/20385879
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2010-5-20
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| pubmed:abstractText |
Although adoptive immunotherapy with CD8(+) CTL is providing clinically relevant results against EBV-driven malignancies, the effector role of CD4(+) T cells has been poorly investigated. We addressed this issue in a lymphoblastoid cell line-induced mouse model of posttransplant lymphoproliferative disease (PTLD) by comparing the therapeutic efficacy of EBV-specific CD4(+) and CD8(+) T cell lines upon adoptive transfer. CD4(+) T cells disclosed a long-lasting and stronger proliferative potential than CD8(+) T cells, had a similar activation and differentiation marker profile, efficiently killed their targets in a MHC class II-restricted manner, and displayed a lytic machinery comparable to that of cognate CD8(+) T cells. A detailed analysis of Ag specificity revealed that CD4(+) T cells potentially target EBV early lytic cycle proteins. Nonetheless, when assessed for the relative therapeutic impact after in vivo transfer, CD4(+) T cells showed a reduced activity compared with the CD8(+) CTL counterpart. This feature was apparently due to a strong and selective downmodulation of MHC class II expression on the tumor cells surface, a phenomenon that could be reverted by the demethylating agent 5-aza-2'-deoxycytidine, thus leading to restoration of lymphoblastoid cell line recognition and killing by CD4(+) T cells, as well as to a more pronounced therapeutic activity. Conversely, immunohistochemical analysis disclosed that HLA-II expression is fully retained in human PTLD samples. Our data indicate that EBV-specific cytotoxic CD4(+) T cells are therapeutic in mice bearing PTLD-like tumors, even in the absence of CD8(+) T cells. These findings pave the way to use cultures of pure CD4(+) T cells in immunotherapeutic approaches for EBV-related malignancies.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
15
|
| pubmed:volume |
184
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5895-902
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| pubmed:meshHeading |
pubmed-meshheading:20385879-Animals,
pubmed-meshheading:20385879-CD4-Positive T-Lymphocytes,
pubmed-meshheading:20385879-CD8-Positive T-Lymphocytes,
pubmed-meshheading:20385879-Callithrix,
pubmed-meshheading:20385879-Cell Line, Transformed,
pubmed-meshheading:20385879-Cell Line, Tumor,
pubmed-meshheading:20385879-Cytotoxicity Tests, Immunologic,
pubmed-meshheading:20385879-Down-Regulation,
pubmed-meshheading:20385879-Epitopes, T-Lymphocyte,
pubmed-meshheading:20385879-Epstein-Barr Virus Infections,
pubmed-meshheading:20385879-HLA-DR Antigens,
pubmed-meshheading:20385879-Herpesvirus 4, Human,
pubmed-meshheading:20385879-Histocompatibility Antigens Class I,
pubmed-meshheading:20385879-Humans,
pubmed-meshheading:20385879-Immunotherapy, Adoptive,
pubmed-meshheading:20385879-Lymphoma, B-Cell,
pubmed-meshheading:20385879-Mice,
pubmed-meshheading:20385879-Mice, SCID
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Virus-specific cytotoxic CD4+ T cells for the treatment of EBV-related tumors.
|
| pubmed:affiliation |
Department of Oncology and Surgical Sciences, University of Padova, Italy.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|