TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation

Nat Commun. 2017 May 3:8:15050. doi: 10.1038/ncomms15050.

Abstract

Differentiation and fate of virus-specific CD8+ T cells after cessation of chronic antigen stimulation is unclear. Here we show that a TCF1+CD127+PD1+ hepatitis C virus (HCV)-specific CD8+ T-cell subset exists in chronically infected patients with phenotypic features of T-cell exhaustion and memory, both before and after treatment with direct acting antiviral (DAA) agents. This subset is maintained during, and for a long duration after, HCV elimination. After antigen re-challenge the less differentiated TCF1+CD127+PD1+ population expands, which is accompanied by emergence of terminally exhausted TCF1-CD127-PD1hi HCV-specific CD8+ T cells. These results suggest the TCF1+CD127+PD1+ HCV-specific CD8+ T-cell subset has memory-like characteristics, including antigen-independent survival and recall proliferation. We thus provide evidence for the establishment of memory-like virus-specific CD8+ T cells in a clinically relevant setting of chronic viral infection and we uncover their fate after cessation of chronic antigen stimulation, implicating a potential strategy for antiviral immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / immunology*
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / virology
  • Hepatocyte Nuclear Factor 1-alpha / immunology*
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Humans
  • Immunologic Memory / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Young Adult

Substances

  • Antiviral Agents
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha