Accumulation of dysfunctional effector CD8+T cells in the liver of patients with chronic HCV infection

Carla Nisii, Massimo Tempestilli, Chiara Agrati, Fabrizio Poccia, Guido Tocci, Maria Antonella Longo, Gianpiero D'Offizi, Roberto Tersigni, Oreste Lo Iacono, Giorgio Antonucci, Alessandra Oliva

Research output: Contribution to journalArticle

Abstract

Background/Aims: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. Methods: Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNγ and TNFα production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. Results: Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7-CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT1.5×N U/ml, and is not evident after mitogen stimulation. Conclusions: The present study describes the accumulation of hypo-responsive CD8+T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment.

Original languageEnglish
Pages (from-to)475-483
Number of pages9
JournalJournal of Hepatology
Volume44
Issue number3
DOIs
Publication statusPublished - Mar 2006

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Keywords

  • Acquired immunity
  • CD8 T lymphocytes
  • Chronic hepatitis
  • IFNγ

ASJC Scopus subject areas

  • Gastroenterology

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