Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Immunol. Aug 15, 2023; 13(2): 11-22
Published online Aug 15, 2023. doi: 10.5411/wji.v13.i2.11
Stem cell-like memory T cells: Role in viral infections and autoimmunity
Meenakshi Sachdeva, Shivangi Taneja, Naresh Sachdeva
Meenakshi Sachdeva, Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
Shivangi Taneja, Naresh Sachdeva, Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India
Author contributions: Sachdeva M co-conceptualized the idea, performed the literature search, and wrote the manuscript; Taneja S supported in literature search, manuscript writing, and formatting; Sachdeva N conceptualized the idea, and supervised and edited the manuscript; and all authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no competing interests.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Naresh Sachdeva, MSc, PhD, Professor, Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh 160012, India.
Received: April 28, 2023
Peer-review started: April 28, 2023
First decision: May 30, 2023
Revised: July 6, 2023
Accepted: July 27, 2023
Article in press: July 27, 2023
Published online: August 15, 2023

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.

Keywords: Stem cell-like memory T cells, Viral infections, Autoimmune diseases, Effector T cells, Memory T cells

Core Tip: This article discusses the contrasting roles of stem cell-like memory T (TSCM) cells during chronic viral infections and autoimmune diseases. During chronic viral infections, such as human immunodeficiency virus-1, the TSCM cells serve as reservoirs for latent viruses, which can be activated to make them susceptible to cytotoxic T cell responses. However, during acute viral infections, the TSCM cells have the ability to replenish the diminished effector T cell population. In autoimmune diseases, like type-1 diabetes, these cells contribute to the disease pathogenesis by persistent generation of autoreactive effector T cells. A better understanding of the key signaling pathways and mediators regulating TSCM cells could lead to novel approaches to target or manipulate these cells for immunotherapeutic applications.