Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
The Second Clinical Medicine School, Nanchang University, Nanchang, China.
Front Endocrinol (Lausanne). 2024 May 10;15:1377322. doi: 10.3389/fendo.2024.1377322. eCollection 2024.
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.
1 型糖尿病（T1D）是一种由胰腺β细胞破坏引起的器官特异性自身免疫性疾病，主要由自身反应性 CD8+T 细胞介导。已经表明，仅需要少量干细胞样β细胞特异性 CD8+T 细胞即可将正常小鼠转化为 T1D 小鼠；因此，通过调节或改变自身反应性 CD8+T 细胞，T1D 可能被治愈或显著改善。然而，干细胞样、效应和耗竭的 CD8+T 细胞在 T1D 中发挥着复杂而重要的作用。高度多样化的 T 细胞受体（TCRs）也使得精确和稳定的靶向治疗更加困难。因此，本综述将探讨自身免疫性 CD8+T 细胞和 TCR 在 T1D 中的作用机制，以及相关的单细胞 RNA 测序（ScRNA-Seq）、CRISPR/Cas9、嵌合抗原受体 T 细胞（CAR-T）和 TCR 基因工程 T 细胞（TCR-T），以进行详细和清晰的概述。本综述强调，靶向 CD8+T 细胞及其 TCR 可能是预测或治疗 T1D 的一种潜在策略。
