Characteristics of CD8 Stem Cell-Like Memory T Cell Subset in Chronic Hepatitis C Virus Infection.

The dysfunction of memory CD8 T cell cannot be reverted by successful clearance of hepatitis C virus (HCV) after direct-acting antivirals (DAAs) therapy, increasing the risk of reinfection with HCV. Stem cell-like memory T cells (Tscm) with superior properties of long-lasting, self-renewing, and multipotency contribute to the maintenance of immune function. We investigated the impact of HCV infection on CD8 Tscm, and their possible role in disease progression, by using DAA-naive HCV-infected and human immunodeficiency virus (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. We observed that the proportion of CD8 Tscm increased in both HCV and HIV/HCV individuals. The proportion of CD8 Tscm had positive and negative correlation with CD8 Tcm (central memory T cells) and CD8 Tem (effector memory T cell), respectively, 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 infection, which suggested that CD8 Tscm is likely associated with effective control of HCV replication for protective immunity. Considering the characteristics of Tscm, our current findings provide implications for Tscm-based vaccine design and immunotherapy development to achieve HCV elimination.