Memory-like HCV-specific CD8+ T cells retain a chronic scar after cure of chronic HCV infection
Chronic hepatitis C virus (HCV) infection is associated with CD8+ T-cell exhaustion characterized by limited effector functions and thus compromised anti-viral activity. Exhausted HCV-specific CD8+ T cells are comprised of memory-like and terminally exhausted CD8+ T-cell subsets. So far, little is not known about the molecular profile and fate of these cells after elimination of chronic antigen stimulation by direct acting antiviral therapy (DAA). Here, we report an antigen-driven molecular core signature underlying exhausted CD8+ T-cell subset heterogeneity in chronic viral infection with a progenitor/progeny relationship of memory-like and terminally exhausted HCV-specific CD8+ T cells via an intermediate stage. Furthermore, transcriptional profiling reveals that the memory-like cells remain after DAA-mediated cure while terminally exhausted HCV-specific CD8+ T-cell subsets are lost. Thus, the memory polarization of the overall HCV-specific CD8+ T-cell response after cure does not result from re-differentiation of exhausted T cells. Consequently, antigen elimination has little impact on the exhausted core signature of memory-like CD8+ T cells that remains clearly different from bona fide T-cell memory. These results identify a molecular signature of T-cell exhaustion that is imprinted like a chronic scar in HCV-specific CD8+ T cells even after HCV cure, highlighting the requirement of re-programming to elicit full effector potential of exhausted T cells.
- 19 samples
- DAC: EGAC00001001656
- Technology: NextSeq 500
- HMB DUO:0000006 (version: 2019-01-07)health or medical or biomedical researchThis data use permission indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry.
- RU DUO:0000014 (version: 2019-01-07)research use onlyThis data use limitation indicates that use is limited to research purposes (e.g., does not include its use in clinical care).
- IRB DUO:0000021 (version: 2019-01-07)ethics approval requiredThis data use modifier indicates that the requestor must provide documentation of local IRB/ERB approval.
DAA for all studies executed in the AG Liver Immunology of the University Hospital Freiburg, Internal Medicine II
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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
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|19 Files (95.1 GB)|