Stem cell-like memory T cells: A perspective from the dark side

Much attention has been paid to a newly discovered subset of memory T (T_M) cells-stem cell-like memory T (T_SCM) cells for their high self-renewal ability, multi-differentiation potential and long-term effector function in adoptive therapy against tumors. Despite their application in cancer therapy, an excess of T_SCM cells also contributes to the persistence of autoimmune diseases for their immune memory and HIV infection as a long-lived HIV reservoir. Signaling pathways Wnt, AMPK/mTOR and NF-κB are key determinants for T_M cell generation, maintenance and proinflammatory effect. In this review, we focus on the phenotypic and functional characteristics of T_SCM cells and discuss their role in autoimmune diseases and HIV-1 chronic infection. Also, we explore the potential mechanism and signaling pathways involved in immune memory and look into the future therapy strategies of targeting long-lived T_M cells to suppress pathogenic immune memory.