Apoptotic epitope-specific CD8+ T cells and interferon signaling intersect in chronic Hepatitis C virus infection

Helene Martini, Alessandra Citro, Carmela Martire, Gabriella D'ettorre, Giancarlo Labbadia, Daniele Accapezzato, Silvia Piconese, Paolo De Marzio, Eugenio N. Cavallari, Ludovica Calvo, Fabiana Rizzo, Martina Severa, Eliana M. Coccia, Gian Luca Grazi, Simona Di Filippo, John Sidney, Vincenzo Vullo, Alessandro Sette, Vincenzo Barnaba

Research output: Contribution to journalArticlepeer-review

Abstract

CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope-specific and hepatitis C virus (HCV)-specific CD8+ T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA+ cell subsets expressing a dysfunctional T-helper 1-like signature program in chronic HCV infection. However, apoptotic epitope-specific CD8+ T cells produced tumor necrosis factor α and interleukin 2 at the intrahepatic level significantly more than HCV-specific CD8+ T cells, despite both populations expressing high levels of programmed death 1 receptor. Contextually, only apoptotic epitope-specific CD8+ T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Together, these data suggest that, compared with HCV-specific CD8+ T cells, apoptotic epitope-specific CD8+ T cells can better sustain chronic immune activation, owing to their capacity to produce tumor necrosis factor α, and exhibit greater resistance to inhibitory signals during chronic HCV infection.

Original languageEnglish
Pages (from-to)674-683
Number of pages10
JournalJournal of Infectious Diseases
Volume213
Issue number4
DOIs
Publication statusPublished - Feb 15 2016

Keywords

  • apoptosis
  • CD8+ T cells
  • chronic immune activation
  • hepatitis C virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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