Phenotype of Memory HCV CD8+ T Cells in Chronic HCV

Abstract

Background Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide. 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 present study is to find out the phenotype pattern of HCV specific memory CD8+ T cells in chronic HCV patients in comparison to HCV exposed seronegative high-risk individuals. Patients 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. Both groups were subjected to carboxyfluorescein diacetate succinimidyl ester (CFSE) proliferation assay in response to HCV specific peptides. Group II was divided into 2 subgroups according to proliferation index (cut-off<2) into, proliferation index +ve high-risk group (+PIHRG) (20 healthcare workers) and proliferation index -ve high-risk group (-PIHRG) (20 healthcare workers). Then flow cytometric analysis of HCV specific CD8+ T cells was done for the all subjects to determine the expression of CD127, CCR7, CD45RO and CD45RA on both proliferating and non-proliferating fractions of cells. Results We found that expression of CD45RA was significantly increased and CCR7 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 reencounter with the antigen. So, chronic HCV patients in our study showed predominance of less differentiated effector memory phenotype (CD45RA+, CCR7-) in peripheral blood in comparison to HCV exposed seronegative high-risk individuals who don’t show overt infection.