CD8(+) T cells armed with retrovirally transduced IFN-gamma.
dc.contributor.author | Becker, Christian | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Jablonska, Jadwiga | |
dc.contributor.author | Bauer, Heike | |
dc.contributor.author | Weiss, Siegfried | |
dc.date.accessioned | 2007-07-23T11:38:53Z | |
dc.date.available | 2007-07-23T11:38:53Z | |
dc.date.issued | 2007-01-01 | |
dc.identifier.citation | J. Mol. Med. 2007, 85(1):63-73 | en |
dc.identifier.issn | 0946-2716 | |
dc.identifier.pmid | 17109130 | |
dc.identifier.doi | 10.1007/s00109-006-0107-8 | |
dc.identifier.uri | http://hdl.handle.net/10033/12858 | |
dc.description.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. | |
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dc.language.iso | en | en |
dc.title | CD8(+) T cells armed with retrovirally transduced IFN-gamma. | en |
dc.type | Article | en |
dc.format.dig | YES | |
refterms.dateFOA | 2018-06-13T00:06:40Z | |
html.description.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. |