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.