scholarly journals Activated T Cells and Soluble Molecules in the Portal Venous Blood of Patients with Cholestatic and Hepatitis C Virus-Positive Liver Cirrhosis. Possible Promotion of Fas/FasL-Mediated Apoptosis in the Bile-Duct Cells and Hepatocyte Injury

2003 ◽  
Vol 31 (3) ◽  
pp. 170-180 ◽  
Author(s):  
N Ariki ◽  
Y Morimoto ◽  
T Yagi ◽  
T Oyama ◽  
Y Cyouda ◽  
...  
Keyword(s):  
T Cells ◽  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Bile Duct ◽  
Venous Blood ◽  
Activated T Cells ◽  
Peripheral Venous Blood ◽  
Nk T Cells ◽  
Portal Venous Blood

We investigated the immune responses of patients with cholestatic and hepatitis C virus-positive (HCV-positive) liver cirrhosis by analysing T-cell subsets and cytokine levels in the portal and peripheral veins, using flow cytometry and enzyme-linked immunosorbent assay. In cholestatic liver cirrhosis, the proportion of natural-killer (NK) T cells and interleukin (IL) 6 and IL-18 levels in the portal venous blood were significantly higher than those in the peripheral venous blood. In HCV-positive liver cirrhosis, the proportions of NK T cells and Fas+ T cells and IL-6 and soluble Fas levels in the portal venous blood were significantly higher than those in the peripheral venous blood. These results suggest that in these diseases, activated T cells and soluble molecules in portal venous blood may promote Fas/FasL-mediated apoptosis of the bile-duct cells and hepatocytes, and contribute to the deterioration in liver function as an inevitable result of positive feedback.

scholarly journals Upregulation of Indoleamine 2,3-Dioxygenase in Hepatitis C Virus Infection

2007 ◽  
Vol 81 (7) ◽  
pp. 3662-3666 ◽  
Author(s):  
Esther Larrea ◽  
José I. Riezu-Boj ◽  
Lucía Gil-Guerrero ◽  
Noelia Casares ◽  
Rafael Aldabe ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Activated T Cells ◽  
Cell Reactivity ◽  
Hepatic Expression ◽  
Indoleamine 2,3 Dioxygenase ◽  
Huh7 Cells ◽  
T Cell Reactivity ◽  
Chronic Hcv

ABSTRACT Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection.

scholarly journals Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses

2005 ◽  
Vol 79 (4) ◽  
pp. 2230-2239 ◽  
Author(s):  
Sara Sundström ◽  
Seisuke Ota ◽  
Lina Y. Dimberg ◽  
Maria G. Masucci ◽  
Anders Bergqvist
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Map Kinase ◽  
Core Protein ◽  
Interleukin 2 ◽  
Mitogen Activated Protein Kinase ◽  
Activated T Cells ◽  
Jnk Signaling ◽  
Mitogen Activated Protein

ABSTRACT Alterations of cytokine responses are thought to favor the establishment of persistent hepatitis C virus (HCV) infections, enhancing the risk of liver cirrhosis and hepatocellular carcinoma. Here we demonstrate that the expression of the HCV core (C) protein in stably transfected T cells correlates with a selective reduction of interleukin-2 (IL-2) promoter activity and IL-2 production in response to T-cell receptor triggering, whereas the activation of IL-4, IL-10, gamma interferon, and tumor necrosis factor alpha was moderately increased. This altered cytokine expression profile was associated with a perturbation of mitogen-activated protein (MAP) kinase responses. Extracellular regulated kinase and p38 were constitutively phosphorylated in C-expressing cells, while triggering of the costimulatory c-Jun N-terminal kinase (JNK) signaling cascade and activation of the CD28 response element within the IL-2 promoter appeared to be impaired. The perturbations of MAP kinase phosphorylation could be eliminated by cyclosporine A-mediated inhibition of nuclear factor of activated T cells, suggesting that the inactivation of JNK signaling and hyporesponsiveness to IL-2 induction were downstream consequences of C-induced Ca2+ flux in a manner that mimics the induction of clonal anergy.

Detection of naïve hepatitis C virus-specific CD8+ T cells in chronically infected patients

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
J Schmidt ◽  
DA Price ◽  
C Neumann-Haefelin ◽  
HE Blum ◽  
R Thimme
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cd8 T Cells

Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

2021 ◽  
Author(s):  
Haidi Karam-Allah Ramadan ◽  
Gamal Badr ◽  
Nancy K Ramadan ◽  
Aml Sayed
Keyword(s):  
Immune Response ◽  
Liver Cirrhosis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Signaling Pathways ◽  
Liver Diseases ◽  
Stat Signaling ◽  
Chronic Hcv ◽  
Direct Acting

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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