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

• Published in: Journal of hepatology Vol. 44; no. 3; pp. 475 - 483
• Main Authors: Nisii, Carla, Tempestilli, Massimo, Agrati, Chiara, Poccia, Fabrizio, Tocci, Guido, Longo, Maria Antonella, D'Offizi, Gianpiero, Tersigni, Roberto, Lo Iacono, Oreste, Antonucci, Giorgio, Oliva, Alessandra
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01-03-2006; Elsevier
• Subjects: Acquired immunity; Adult; Aged; Apoptosis; Biological and medical sciences; CD8 T lymphocytes; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Chronic hepatitis; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - metabolism; Hepatitis C, Chronic - pathology; Human viral diseases; Humans; IFNγ; Infectious diseases; Interferon-gamma - metabolism; Liver - metabolism; Liver - pathology; Male; Medical sciences; Membrane Glycoproteins - metabolism; Middle Aged; Perforin; Phenotype; Pore Forming Cytotoxic Proteins; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology; Tumor Necrosis Factor-alpha - metabolism; Viral diseases; Viral hepatitis; IFNγ; Acquired immunity; CD8 T lymphocytes; Chronic hepatitis; Human; Hepatic disease; Effector; Accumulation; Infection; Chronic; Viral disease; Gastroenterology; Digestive diseases; Viral hepatitis C
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.10.023

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.
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.
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 ALT<1.5×N than with ALT>1.5×N
U/ml, and is not evident after mitogen stimulation.
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.