6533b856fe1ef96bd12b1c7e

RESEARCH PRODUCT

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

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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 ALT 1.5×NU/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.