الفهرس 
Hepatitis C virus.Only 14 pages are availabe for public view
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Abstract
Abstract
Background: Worldwide, 170 million people are infected with Hepatitis C Virus (HCV); 71 million individuals are chronically infected with important variations according to the geographical area. After acute infection, a majority of healthy adults will develop persistent viremia. An infection with HCV activates the immune system to defend the host with a broad range of innate and adaptive immune responses. Cellular immune response shows antiviral immunity by means of virus specific CD8+ T cytotoxic lymphocytes and CD4+ T helper cells. After resolution of infection, a population of the virus-specific memory CD8+ T cells protects the host against reinfection. These subsets of memory cells differ with respect to their anatomical localization, their phenotype and their protective potential. Objectives: The aim of the current study is to identify the role of memory markers (CD127, CCR7, CD45RA and CD45RO) expressed on the CD8+ T cells in the clearance of HCV infection through studying the chronic HCV patients versus seronegative high-risk individuals. Subjects and methods: This case control study included 60 individuals categorized into two main groups, (group I) included 20 chronic HCV patients and (group II= control group) included 40 HCV seronegative healthcare workers (HCWs). Both groups were subjected to flow cytometric analysis of Peripheral blood mononuclear cell (PBMC) to determine the percentage of expression of CD3, CD8 and CD127 markers on CD8+ T cells. PBMC from both groups were subjected to carboxyfluorescien diacetate succinimidyl ester (CFSE) proliferation assay in response to HCV specific peptides (core, NS3/NS4, NS5). The second group was divided into 2 subgroups according to proliferation index (cut-off<2) into: proliferation index +ve high-risk group (+PIHRG) (20 HCWs) and proliferation index -ve high-risk group (-PIHRG) (20 HCWs). Then Flow cytometric analysis of HCV specific CD8+ T cells was done for all subjects in the three groups (chronic HCV patients, “+PIHRG”, “-PIHRG”) to determine the expression of CD127,CCR7,CD45RO and CD45RA on both proliferating and non-proliferating fractions of HCV specific CD8+ T cells.
Results: We found that expression of CD45RA “marker of early-differentiated memory CD8+ T cells” was significantly increased and CCR7 “marker of central memory CD8+ T cells” was significantly decreased on HCV CD8+ T cells in the chronic HCV group than in the high risk groups in response to different HCV peptides. Conclusion: During persistent viremia in chronic HCV infection, subthreshold signal levels established by HCV different proteins provide anergy of virus specific memory CD8+ T cells that are unable to differentiate into full effector cells upon a possible re-encounter with the antigen. So, chronic HCV patients in our study showed predominance of less differentiated central memory phenotype (CD45RA+) in peripheral blood in comparison to HCV exposed seronegative high-risk individuals who showed predominance of (CD45RO+, CCR7+) memory phenotype. It seems that in high risk group individuals the continuous low level exposure to HCV creates waves of effector memory cytotoxic T cells that are capable of clearing the virus while in chronic infection there are long-lived memory cells that are ineffective in clearing the virus.