CD8+ stem cell-like memory T cell subset is associated with disease progression in chronic hepatitis C virus infection

Abstract Background The dysfunction of memory CD8+T cell can not be reverted by successful clearance of hepatitis C virus (HCV) after direct-acting antivirals (DAA) therapy, increasing the risk of reinfection with HCV. Stem cell-like memory T cells (Tscm) with superior capacities of long-lasting, self-renewing, and multipotency that contribute to the maintenance of immune function. Methods We investigated the impact of HCV infection on CD8+Tscm, and the possible role this compartment may has in disease progression, by using DAA-naïve HCV monoinfected and HIV/HCV coinfected cohorts. The distribution of memory CD8+T cell subsets and the level of T cell immune activation were determined by flow cytometry. Associations between CD8+Tscm and other memory T cell subsets, HCV viral load, as well as the level of T cell immune activation were analyzed. Results We observed that the proportion of CD8+Tscm increased in both HCV and HIV/HCV individuals. The proportion of CD8+Tscm had a positive correlation with that of CD8+Tcm, and a negative correlation with that of CD8+Tem, representing the contribution of CD8+Tscm in T cell homeostasis. In addition, higher frequency of CD8+Tscm indicated lower HCV viral load and less T cell immune activation in HCV monoinfection, which suggested that CD8+Tscm may associate with effective control of HCV replication. Conclusions CD8+Tscm may has protective immunity to HCV infection. Considering the characteristics of Tscm, our current study opens new opportunity for Tscm-based vaccine design and immunotherapy development to achieve HCV elimination.