CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression

PLoS Pathog. 2014 Sep 25;10(9):e1004380. doi: 10.1371/journal.ppat.1004380. eCollection 2014 Sep.

Abstract

Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / metabolism
  • Cytomegalovirus Infections / virology
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / metabolism
  • Epstein-Barr Virus Infections / virology
  • Flow Cytometry
  • GPI-Linked Proteins / metabolism
  • Hepacivirus / physiology
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism
  • Hepatitis C / virology
  • Herpesvirus 4, Human / physiology
  • Humans
  • Lymphocyte Activation
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, Immunologic / metabolism*

Substances

  • Antigens, CD
  • CD160 protein, human
  • GPI-Linked Proteins
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic

Grant support

This work was funded by the Swiss National Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.