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

Hensel, N., Gu, Z., Sagar, S., Wieland, D., Jechow, K., Kemming, J., et al. (2021). Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection. Nature Immunology, 22, 229-239. doi: 10.1038/s41590-020-00817-w.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-AB2D-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-ED3B-D
Genre: Journal Article

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 Creators:
Hensel, Nina1, Author
Gu, Zuguang1, Author
Sagar, Sagar1, 2, Author
Wieland, Dominik1, Author
Jechow, Katharina1, Author
Kemming, Janine1, Author
Llewellyn-Lacey, Sian1, Author
Gostick, Emma1, Author
Sogukpinar, Oezlem1, Author
Emmerich, Florian1, Author
Price, David A1, Author
Bengsch, Bertram1, Author
Boettler, Tobias1, Author
Neumann-Haefelin, Christoph1, Author
Eils, Roland1, Author
Conrad, Christian1, Author
Bartenschlager, Ralf1, Author
Grün, Dominic2, Author              
Ishaque, Naveed1, Author
Thimme, Robert1, Author
Hofmann, Maike1, Author more..
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243642              

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 Abstract: In chronic hepatitis C virus (HCV) infection, exhausted HCV-specific CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cell response. However, an exhausted core signature of memory-like CD8<sup>+<sup> T cells was still detectable, including, to a smaller extent, in HCV-specific CD8<sup>+</sup> 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<sup>+</sup> T cells even after the cessation of chronic antigen stimulation.

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Language(s): eng - English
 Dates: 2021-01-04
 Publication Status: Published online
 Pages: -
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41590-020-00817-w
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Title: Nature Immunology
  Other : Nat. Immunol.
Source Genre: Journal
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Publ. Info: New York, NY : Nature America Inc.
Pages: - Volume / Issue: 22 Sequence Number: - Start / End Page: 229 - 239 Identifier: ISSN: 1529-2908
CoNE: https://pure.mpg.de/cone/journals/resource/974392607073