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

Abstract

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.