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

Hensel N, Gu Z, Sagar , Wieland D, Jechow K, Kemming J, Llewellyn-Lacey S, Gosticle E, Sogukpinar O, Emmerich F, Price DA, Bengsch B, Boettler T, Neumann-Haefelin C, Eils R, Conrad C, Bartenschlager R, Gruen D, Ishaque N, Thimme R, Hofmann M (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Nature Immunology Nature Research

Book Volume: 22

Pages Range: 229-239

Journal Issue: 2

DOI: 10.1038/s41590-020-00817-w

Abstract

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.

Involved external institutions

Universitätsklinikum Freiburg DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Cardiff University GB United Kingdom (GB) Albert-Ludwigs-Universität Freiburg DE Germany (DE) Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Max-Planck-Institut für Immunbiologie und Epigenetik (MPI-IE) / Max Planck Institute of Immunobiology and Epigenetics DE Germany (DE)

How to cite

APA:

Hensel, N., Gu, Z., Sagar, ., Wieland, D., Jechow, K., Kemming, J.,... Hofmann, M. (2021). Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection. Nature Immunology, 22(2), 229-239. https://doi.org/10.1038/s41590-020-00817-w

MLA:

Hensel, Nina, et al. "Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection." Nature Immunology 22.2 (2021): 229-239.

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