Central memory T cells: stem-like biology, pathogenic roles in autoimmunity, and therapeutic applications

Central memory T (TCM) cells are a cornerstone of the adaptive immune system, serving as a long-lived, self-renewing stem-like population that provides durable immunological protection. Primarily residing in secondary lymphoid organs, TCM cells are characterised by robust proliferative potential, multipotent differentiation capacity, and metabolic reliance on oxidative phosphorylation. These attributes are crucial for mediating rapid and effective secondary immune responses.Recent advances have elucidated the complex molecular circuitry governing TCM cells' fate decisions, focusing on the transcription factor networks and epigenetic modifications that preserve their characteristic stemness. In the context of disease, TCM cells play a dual role: they are a vital source of effector cells for combating infections and malignancies, yet they can also contribute to the chronic inflammation that drives autoimmune disorders including systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, and Sjögren's disease.This functional dichotomy underlies their considerable clinical significance. Notably, TCM cells represent a preferred cellular source for chimeric antigen receptor T (CAR-T) cell therapy in both oncology and emerging autoimmune indications, serve as a predictive biomarker for the efficacy of immune checkpoint inhibitors, and act as a key indicator of vaccine effectiveness.This review comprehensively examines TCM cells, covering their biological features, developmental mechanisms, and recent clinical applications in cancer immunotherapy, autoimmune diseases, and cellular therapies, while outlining future therapeutic directions.