Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation

PLoS Pathog. 2010 Jun 10;6(6):e1000947. doi: 10.1371/journal.ppat.1000947.


Exhausted CD8+ T cell responses during chronic viral infections are defined by a complex expression pattern of inhibitory receptors. However, very little information is currently available about the coexpression patterns of these receptors on human virus-specific CD8+ T cells and their correlation with antiviral functions, T cell differentiation and antigen recognition. We addressed these important aspects in a cohort of 38 chronically HCV infected patients and found a coexpression of inhibitory receptors such as 2B4, CD160 and KLRG1 in association with PD-1 in about half of the HCV-specific CD8+ T cell responses. Importantly, this exhaustive phenotype was associated with low and intermediate levels of CD127 expression, an impaired proliferative capacity, an intermediate T cell differentiation stage and absence of sequence variations within the corresponding epitopes, indicating ongoing antigen triggering. In contrast, a low expression of inhibitory receptors by the remaining HCV-specific CD8+ T cells occurred in concert with a CD127hi phenotype, an early T cell differentiation stage and presence of viral sequence variations within the corresponding epitopes. In sum, these results suggest that T cell exhaustion contributes to the failure of about half of HCV-specific CD8+ T cell responses and that it is determined by a complex interplay of immunological (e.g. T cell differentiation) and virological (e.g. ongoing antigen triggering) factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation*
  • Cell Proliferation
  • Flow Cytometry
  • GPI-Linked Proteins
  • Hepacivirus / isolation & purification
  • Hepatitis C / immunology*
  • Hepatitis C / virology
  • Humans
  • Lectins, C-Type / metabolism*
  • Lymphocyte Activation
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic / metabolism*
  • Signaling Lymphocytic Activation Molecule Family
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Trans-Activators / metabolism*
  • Viral Load


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • CD160 protein, human
  • CD244 protein, human
  • GPI-Linked Proteins
  • KLRG1 protein, human
  • Lectins, C-Type
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • Trans-Activators