Autoimmune CD8+ T cells in type 1 diabetes: from single-cell RNA sequencing to T-cell receptor redirection

• Published in: Frontiers in endocrinology (Lausanne) 2024, Vol.15, p.1377322-1377322
• Main Authors: Yang, Kangping, Zhang, Yihan, Ding, Jiatong, Li, Zelin, Zhang, Hejin, Zou, Fang
• Format: Article
• Language: English
• Subjects: Animals; Autoimmunity; CD8+ T cells; CD8-Positive T-Lymphocytes - immunology; chimeric antigen receptor T-cell (CAR-T); CRISPR/Cas9; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Humans; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - metabolism; Mice; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Sequence Analysis, RNA - methods; Single-Cell Analysis - methods; single-cell RNA sequencing (scRNA-seq); type 1 diabetes
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2024.1377322

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by pancreatic β cell destruction and mediated primarily by autoreactive CD8+ T cells. It has been shown that only a small number of stem cell-like β cell-specific CD8+ T cells are needed to convert normal mice into T1D mice; thus, it is likely that T1D can be cured or significantly improved by modulating or altering self-reactive CD8+ T cells. However, stem cell-type, effector and exhausted CD8+ T cells play intricate and important roles in T1D. The highly diverse T-cell receptors (TCRs) also make precise and stable targeted therapy more difficult. Therefore, this review will investigate the mechanisms of autoimmune CD8+ T cells and TCRs in T1D, as well as the related single-cell RNA sequencing (ScRNA-Seq), CRISPR/Cas9, chimeric antigen receptor T-cell (CAR-T) and T-cell receptor-gene engineered T cells (TCR-T), for a detailed and clear overview. This review highlights that targeting CD8+ T cells and their TCRs may be a potential strategy for predicting or treating T1D.