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Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection

Hensel, Nina, Gu, Zuguang, Sagar, Wieland, Dominik, Jechow, Katharina, Kemming, Janine, Llewellyn-Lacey, Sian, Gostick, Emma, Sogukpinar, Oezlem, Emmerich, Florian, Price, David A., Bengsch, Bertram, Boettler, Tobias, Neumann-Haefelin, Christoph, Eils, Roland, Conrad, Christian, Bartenschlager, Ralf, Grün, Dominic, Ishaque, Naveed, Thimme, Robert and Hofmann, Maike 2021. Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection. Nature Immunology 22 (2) , 229–239. 10.1038/s41590-020-00817-w

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In chronic hepatitis C virus (HCV) infection, exhausted HCV-specific CD8+ T cells comprise memory-like and terminally exhausted subsets. However, little is known about the molecular profile and fate of these two subsets after the elimination of chronic antigen stimulation by direct-acting antiviral (DAA) therapy. Here, we report a progenitor–progeny relationship between memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate subset. Single-cell transcriptomics implicated that memory-like cells are maintained and terminally exhausted cells are lost after DAA-mediated cure, resulting in a memory polarization of the overall HCV-specific CD8+ T cell response. However, an exhausted core signature of memory-like CD8+ T cells was still detectable, including, to a smaller extent, in HCV-specific CD8+ T cells targeting variant epitopes. These results identify a molecular signature of T cell exhaustion that is maintained as a chronic scar in HCV-specific CD8+ T cells even after the cessation of chronic antigen stimulation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of Acceptance: 6 October 2020
Last Modified: 30 Jan 2022 10:52

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