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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2006-3-7
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pubmed:databankReference |
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pubmed:abstractText |
CD8+ T cells can mediate eradication of established tumors, and strategies to amplify tumor-reactive T-cell numbers by immunization or ex vivo expansion followed by adoptive transfer are currently being explored in individuals with cancer. Generating effective CD8+ T cell-mediated responses to tumors is often impeded by T-cell tolerance to relevant tumor antigens, as most of these antigens are also expressed in normal tissues. We examined whether such tolerant T cells could be rescued and functionally restored for use in therapy of established tumors. We used a transgenic T-cell receptor (TCR) mouse model in which peripheral CD8+ T cells specific for a candidate tumor antigen also expressed in liver are tolerant, failing to proliferate or secrete interleukin (IL)-2 in response to antigen. Molecular and cellular analysis showed that these tolerant T cells expressed the IL-15 receptor alpha chain, and could be induced to proliferate in vitro in response to exogenous IL-15. Such proliferation abrogated tolerance and the rescued cells became effective in treating leukemia. Therefore, high-affinity CD8+ T cells are not necessarily deleted by encounter with self-antigen in the periphery, and can potentially be rescued and expanded for use in tumor immunotherapy.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Fasl protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/IL15RA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Il15ra protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:CookeMichael PMP,
pubmed-author:DossettMichelle LML,
pubmed-author:GreenbergPhilip DPD,
pubmed-author:HuangMaria ZMZ,
pubmed-author:MorimotoJunkoJ,
pubmed-author:OhlénClaesC,
pubmed-author:SacksJilian AJA,
pubmed-author:SatherBlythe DBD,
pubmed-author:SuttonSusan ESE,
pubmed-author:TanXiaoxioX,
pubmed-author:TeagueRyan MRM
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
335-41
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:16474399-Animals,
pubmed-meshheading:16474399-Antigens, CD8,
pubmed-meshheading:16474399-CD8-Positive T-Lymphocytes,
pubmed-meshheading:16474399-Cell Proliferation,
pubmed-meshheading:16474399-Fas Ligand Protein,
pubmed-meshheading:16474399-Humans,
pubmed-meshheading:16474399-Immune Tolerance,
pubmed-meshheading:16474399-Immunologic Memory,
pubmed-meshheading:16474399-Immunotherapy, Adoptive,
pubmed-meshheading:16474399-Interleukin-15,
pubmed-meshheading:16474399-Membrane Glycoproteins,
pubmed-meshheading:16474399-Mice,
pubmed-meshheading:16474399-Mice, Inbred C57BL,
pubmed-meshheading:16474399-Mice, Transgenic,
pubmed-meshheading:16474399-Neoplasms,
pubmed-meshheading:16474399-Receptors, Interleukin-15,
pubmed-meshheading:16474399-Receptors, Interleukin-2,
pubmed-meshheading:16474399-Tumor Necrosis Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors.
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pubmed:affiliation |
Department of Immunology, University of Washington School of Medicine, Office H-564 HSC, Box 357650, Seattle, Washington 98195, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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