Hepatitis C virus (HCV) infects millions of people worldwide with the majority of infections becoming chronic. Chronic infection can result in severe morbidity and mortality. Although recently developed therapies are increasingly more effective at clearing virus, many hurdles prevent universal access to treatment. Therefore, a vaccine to prevent progression to chronic disease is an appropriate public health solution. Interestingly, about 25% of initial HCV infections are spontaneously resolved without treatment. However, the immune correlates of protection are not fully elucidated. Individuals who clear the initial infection can become reinfected, but upon reinfection tend to have attenuated viral kinetics, suggesting a role for the adaptive immune response. Clearance of a reinfection models a successful immune response upon re-exposure. In this analysis, we examine the protective role of CD8 T cells during HCV reinfections using a prospective cohort study of individuals at high-risk of acquiring HCV in Baltimore, Maryland. The cellular immune response during reinfection was characterized by assessing breadth, specificity, and magnitude of anti-viral cytokines produced upon recognition of HCV epitopes. We then phenotyped HCV-specific CD8 T cells to examine the dynamics of activation, exhaustion, maturation, and memory of the immune response during reinfection. The results suggest an association between reinfection events and enhanced magnitude and breadth of T cell responses. Additionally, the HCV-specific CD8 T cells are not dampened upon reinfection but are capable of becoming activated and vary in T cell subsets upon reinfection.
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Characterizing CD8+ T cells in Hepatitis C Virus Reinfection
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