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

Hensel, Nina; Gu, Zuguang; Sagar, 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; Hofmann, Maike

doi:10.1038/s41590-020-00817-w

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学術論文

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

MPS-Authors

Sagar, Sagar
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;
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Grün, Dominic
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.nature.com/articles/s41590-020-00817-w
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引用

Hensel, N., Gu, Z., Sagar, S., Wieland, D., Jechow, K., Kemming, J., Llewellyn-Lacey, S., Gostick, E., Sogukpinar, O., Emmerich, F., Price, D. A., Bengsch, B., Boettler, T., Neumann-Haefelin, C., Eils, R., Conrad, C., Bartenschlager, R., Grün, D., Ishaque, N., Thimme, R., & Hofmann, M. (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.

引用: https://hdl.handle.net/21.11116/0000-0007-AB2D-7

要旨

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.