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

National Institute for Infectious Diseases IRCCS L. Spallanzani, Via Portuense 292, 00149 Rome, Italy.
Journal of Hepatology (Impact Factor: 10.4). 04/2006; 44(3):475-83. DOI: 10.1016/j.jhep.2005.10.023
Source: PubMed

ABSTRACT 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, IFNgamma and TNFalpha 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<1.5xN than with ALT>1.5xNU/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.

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    • "Dolganiuc et al found that mDC induced more Tregs in HCV infected individuals, which could hamper T helper responses [29]. Nisii et al found an accumulation of dysfunctional CD8+ T cells in livers of subjects with chronic HCV suggesting global T cell defects may be present [30]. Defects in CD4+ helper T cells have not been reported. "
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