Abstract
Interferon-gamma (IFN-γ) 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-γ in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-γ production can be increased in T cells, we introduced an IFN-γ encoding cDNA into IFN-γ−/− and IFN-γ+/+ CD8+ effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-γ that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-γ mRNA transcription, translation and secretion of IFN-γ protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-γ transduction. Importantly, CD8+ T cells retrovirally transduced with IFN-γ exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-γ−/− mice. Thus, T cells can be readily armed with IFN-γ without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.
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Acknowledgements
The authors thank M. Höxter for excellent cell sorting performance and S. Vorwerk for technical assistance. Helpful discussions by Drs. A. Kroeger and H. Hauser and the critical reading of the manuscript by C. Samuelsson are gratefully acknowledged. This work was supported in part by the Deutsche Forschungsgemeinschaft, the Deutsche Krebshilfe, and the Strategiefonds of the Helmholtz Association.
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Becker, C., Lienenklaus, S., Jablonska, J. et al. CD8+ T cells armed with retrovirally transduced IFN-γ. J Mol Med 85, 63–73 (2007). https://doi.org/10.1007/s00109-006-0107-8
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DOI: https://doi.org/10.1007/s00109-006-0107-8