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 persiste...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 patiets, 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. 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.展开更多
文摘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 patiets, 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. 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.
