2.50
Hdl Handle:
http://hdl.handle.net/10033/12858
Title:
CD8(+) T cells armed with retrovirally transduced IFN-gamma.
Authors:
Becker, Christian; Lienenklaus, Stefan; Jablonska, Jadwiga; Bauer, Heike; Weiss, Siegfried
Abstract:
Interferon-gamma (IFN-gamma) is considered a key cytokine involved in the preventive and defensive responses of T cells against infectious pathogens and tumors. Therefore, the transgenic expression of IFN-gamma in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-gamma production can be increased in T cells, we introduced an IFN-gamma encoding cDNA into IFN-gamma(-/-) and IFN-gamma(+/+) CD8(+) effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-gamma that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-gamma mRNA transcription, translation and secretion of IFN-gamma protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-gamma transduction. Importantly, CD8(+) T cells retrovirally transduced with IFN-gamma exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-gamma(-/-) mice. Thus, T cells can be readily armed with IFN-gamma without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.
Citation:
J. Mol. Med. 2007, 85(1):63-73
Issue Date:
1-Jan-2007
URI:
http://hdl.handle.net/10033/12858
DOI:
10.1007/s00109-006-0107-8
PubMed ID:
17109130
Type:
Article
Language:
en
ISSN:
0946-2716
Appears in Collections:
Publications of RG Mucosal Immunity (MI)

Full metadata record

DC FieldValue Language
dc.contributor.authorBecker, Christian-
dc.contributor.authorLienenklaus, Stefan-
dc.contributor.authorJablonska, Jadwiga-
dc.contributor.authorBauer, Heike-
dc.contributor.authorWeiss, Siegfried-
dc.date.accessioned2007-07-23T11:38:53Z-
dc.date.available2007-07-23T11:38:53Z-
dc.date.issued2007-01-01-
dc.identifier.citationJ. Mol. Med. 2007, 85(1):63-73en
dc.identifier.issn0946-2716-
dc.identifier.pmid17109130-
dc.identifier.doi10.1007/s00109-006-0107-8-
dc.identifier.urihttp://hdl.handle.net/10033/12858-
dc.description.abstractInterferon-gamma (IFN-gamma) is considered a key cytokine involved in the preventive and defensive responses of T cells against infectious pathogens and tumors. Therefore, the transgenic expression of IFN-gamma in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-gamma production can be increased in T cells, we introduced an IFN-gamma encoding cDNA into IFN-gamma(-/-) and IFN-gamma(+/+) CD8(+) effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-gamma that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-gamma mRNA transcription, translation and secretion of IFN-gamma protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-gamma transduction. Importantly, CD8(+) T cells retrovirally transduced with IFN-gamma exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-gamma(-/-) mice. Thus, T cells can be readily armed with IFN-gamma without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.en
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dc.titleCD8(+) T cells armed with retrovirally transduced IFN-gamma.en
dc.typeArticleen
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