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


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<1.5xN than with ALT>1.5xNU/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.
Nisii
Carla
C
National Institute for Infectious Diseases IRCCS L. Spallanzani, Via Portuense 292, 00149 Rome, Italy.
Tempestilli
Massimo
M
Agrati
Chiara
C
Poccia
Fabrizio
F
Tocci
Guido
G
Longo
Maria Antonella
MA
D'Offizi
Gianpiero
G
Tersigni
Roberto
R
Lo Iacono
Oreste
O
Antonucci
Giorgio
G
Oliva
Alessandra
A
D000328:Adult; D000368:Aged; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma