Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection
- 1 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 22 (2), 229-U246
- https://doi.org/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. Thimme and colleagues identify a molecular signature of T cell exhaustion resembling a 'chronic scar' that is imprinted in hepatitis C virus-specific CD8(+) T cells and cannot simply be reversed by viral clearance.Funding Information
- Deutsche Forschungsgemeinschaft (272983813, 272983813, 272983813, 272983813, 272983813, 272983813, GR4980/3-1)
- Wellcome Trust Senior Investigator Award
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