Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection.
Nat Immunol
; 22(2): 229-239, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-33398179
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.
Full text:
1
Database:
MEDLINE
Main subject:
Hepacivirus
/
CD8-Positive T-Lymphocytes
/
Hepatitis C, Chronic
/
Transcriptome
/
Immunologic Memory
Limits:
Humans
Language:
En
Year:
2021
Type:
Article