Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: association with liver disease severity.
OBJECTIVE
It has been suggested that enhanced T-cell apoptosis in hepatitis C virus (HCV) infection may lead to down-regulation of their cellular immune response, thus contributing to the persistency of HCV infection. In the present study we have investigated the role of bcl-2 and nuclear factor kappa B (NFkappaB) in dexamethasone-induced apoptosis of peripheral T cells in chronic HCV infection.


METHODS
The expression of bcl-2 and NFkappaB in peripheral T cells as well as spontaneous and dexamethasone-induced T-cell apoptosis were studied in HCV-infected patients (n=21), hepatitis B virus (HBV)-infected patients (n=14) and healthy individuals (n=19). These parameters were correlated with markers of autoimmunity and disease severity.


RESULTS
NFkappaB, but not bcl-2 expression, was significantly decreased in the HCV-infected patients. This decrease was associated with the presence of mixed cryoglobulins (MC) and rheumatoid factor and was positively correlated with alanine aminotransferase (ALT) levels and histological activity index (HAI). Both spontaneous and dexamethasone-induced T-cell apoptosis were enhanced in HCV-infected patients; however, only the latter was correlated with the presence of MC, ALT levels and HAI.


CONCLUSIONS
We confirm previous reports that enhanced T-cell apoptosis in HCV infection may play an important role in disease severity. Decreased expression of NFkappaB is important in the development of peripheral T-cell apoptosis, thus contributing to viral persistence and autoimmunity in these patients.
Toubi
E
E
Department of Internal Medicine, Bnai-Zion Medical Center, Faculty of Medicine, Technion, 31048, Haifa, Israel. toubi@tx.tecnion.ac.il
Kessel
A
A
Goldstein
L
L
Slobodin
G
G
Sabo
E
E
Shmuel
Z
Z
Zuckerman
E
E
D000328:Adult; D017209:Apoptosis; D023201:CD40 Ligand / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006509:Hepatitis B / Q000503:physiopathology; D019698:Hepatitis C, Chronic / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012016:Reference Values; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D019014:fas Receptor / Q000378:metabolism
D005938:Glucocorticoids; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D023201:CD40 Ligand; D003907:Dexamethasone