Determining antigen-specific T cell phenotypes in cases of Hepatitis C virus clearance versus chronic infection.

Abstract

Abstract Globally, approximately 1.5 million new Hepatitis C virus (HCV) infections occur annually. A vaccine to prevent chronic HCV infection would limit HCV transmission and pathogenesis of HCV. To understand immunity to HCV infection in high risk populations, we prospectively followed HCV antibody negative high-risk people who inject drugs (PWIDs) in a protocol designed for monthly follow-up. We demonstrated previously that HCV reinfection in PWIDs is associated with a reduction in the magnitude and duration of viremia versus the initial infection and broadened cellular immune responses, consistent with protective immunity against chronic disease. We have characterized CD8+ HCV-specific T cells from the acute phase of HCV using high dimensional spectral flow cytometry to define the simultaneous expression of 25 intracellular metabolic and cell surface molecules. We found that HCV-specific CD8+ T cells from those who progress to chronic infection have a unique acute phase phenotype that clusters separately from those who later successfully control HCV. Acute phase CD8+ HCV-specific T cells from those who subsequently clear an initial HCV infection show increased expression of CD127 and CXCR3 and decreased expression of GLUT1, PD-1 and CD39 compared to acute phase T cells in those who later progress to chronic infection. Understanding HCV specific T cell phenotypes in successful control of HCV infection and reinfection will guide goals for vaccine induced immunity to prevent chronic HCV infection. Supported by grants from the NIH (U19 AI159822)