Stem cell-like memory T cells: Role in viral infections and autoimmunity

Stem cell-like memory T (TSCM) cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases. Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization. In case of chronic viral diseases such as human immunodeficiency virus-1, CD4+ TSCM cells, serve as major reservoirs of the latent virus. However, during immune activation and functional exhaustion of effector T cells, these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection. More recently, these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion. Similarly, studies are also investigating their pathological role in driving autoimmune responses. However, there are several gaps in the understanding of the role of TSCM cells in viral and autoimmune diseases to make them potential therapeutic targets. In this minireview, we have attempted an updated compilation of the dyadic role of these complex TSCM cells during such human diseases along with their biology and transcriptional programs.