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CD8+ T Cell Dysfunction in Chronic HCV Infection and its Association with Liver Fibrosis

Infection with hepatitis C virus (HCV) can cause liver damage known as fibrosis, which
often leads to liver disease and hepatocellular carcinoma. The impairment of circulating, bulk
(non-specific and specific) CD8+ T cells within HCV-infection, characterized by an altered
phenotype and the increased expression of pro-apoptotic genes, is observed when compared to
uninfected controls. The relationship between bulk CD8+ T cell function and the extent of liver
damage has not been demonstrated. In this study, widespread immune alterations were observed
in untreated HCV infection with advanced liver fibrosis. Untreated HCV-infected individuals
with advanced fibrosis possessed a significantly decreased proportion of naïve CD8+ T cells and
an increased proportion of late effector memory CD8+ T cells compared to uninfected controls.
Upon T cell receptor (TCR) stimulation, these individuals also had an increased intracellular
IFN-γ expression for four CD8+ T cell subsets, a decreased CD107a expression for central
memory CD8+ T cells, and a decreased perforin induction for naïve and central memory CD8+ T
cells. These immune alterations did not reverse 24 weeks after viral cure. This study indicates
there is a relationship between the differentiation and function of bulk CD8+ T cells and the
extent of liver damage within HCV infection.

Identiferoai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/37345
Date28 March 2018
CreatorsDeonarine, Felicia
ContributorsAngel, Jonathan
PublisherUniversité d'Ottawa / University of Ottawa
Source SetsUniversité d’Ottawa
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Formatapplication/pdf

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