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

Nina HenselZuguang Gunull SagarDominik WielandKatharina JechowJanine KemmingSian Llewellyn-LaceyEmma GostickOezlem SogukpinarFlorian EmmerichDavid A PriceBertram BengschTobias BoettlerChristoph Neumann-HaefelinRoland EilsChristian ConradRalf F W BartenschlagerDominic GrünNaveed IshaqueRobert ThimmeMaike Hofmann
Published in: Nature immunology (2021)
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.
Keyphrases
  • hepatitis c virus
  • human immunodeficiency virus
  • working memory
  • single cell
  • mesenchymal stem cells
  • bone marrow
  • drug induced
  • signaling pathway