Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: Exploring the immunological mechanisms

Vittorio Francavilla, Daniele Accapezzato, Marietta De Salvo, Pisana Rawson, Olivia Cosimi, Martin Lipp, Antonella Cerino, Agostino Cividini, Mario U. Mondelli, Vincenzo Barnaba

Research output: Contribution to journalArticlepeer-review

Abstract

Hallmark of acute hepatitis C virus (HCV) infection is a severe virus-specific effector CD8+ T cell dysfunction that seems to be a critical factor in preventing the resolution of infection and in favoring the onset of chronic liver immunopathology. We suggest that this dysfunction is critical in the establishment of HCV persistence, unless it is compensated by multispecific responses, as found in individuals resolving infection. Analyses on purified populations indicate that central memory HCV-specific CCR7+/CD8+ T cells efficiently proliferate and differentiate in vitro, although the large population of memory effector CCR7- cells found in the peripheral blood of acutely infected patients display poor effector functions ex vivo (semi-effectors). However, we report strong evidence in support of IL-2 being capable of pushing semi-effector CTL to complete their effector cell program. Therefore, IL-2 deficiency during T cell activation may be responsible for the dichotomy between memory CTL expansion and incomplete effector differentiation shown in patients with acute HCV infection. These data are consistent with the possible therapeutic treatment with IL-2 to rebuild the effector T cell pool in these patients.

Original languageEnglish
Pages (from-to)427-437
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number2
DOIs
Publication statusPublished - Feb 2004

Keywords

  • Cellular activation
  • Cellular differentiation
  • CTL
  • Memory

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: Exploring the immunological mechanisms'. Together they form a unique fingerprint.

Cite this