Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
Signal Transduct Target Ther. 2023 Jun 19;8(1):235. doi: 10.1038/s41392-023-01471-y.
T cells are crucial for immune functions to maintain health and prevent disease. T cell development occurs in a stepwise process in the thymus and mainly generates CD4 and CD8 T cell subsets. Upon antigen stimulation, naïve T cells differentiate into CD4 helper and CD8 cytotoxic effector and memory cells, mediating direct killing, diverse immune regulatory function, and long-term protection. In response to acute and chronic infections and tumors, T cells adopt distinct differentiation trajectories and develop into a range of heterogeneous populations with various phenotype, differentiation potential, and functionality under precise and elaborate regulations of transcriptional and epigenetic programs. Abnormal T-cell immunity can initiate and promote the pathogenesis of autoimmune diseases. In this review, we summarize the current understanding of T cell development, CD4 and CD8 T cell classification, and differentiation in physiological settings. We further elaborate the heterogeneity, differentiation, functionality, and regulation network of CD4 and CD8 T cells in infectious disease, chronic infection and tumor, and autoimmune disease, highlighting the exhausted CD8 T cell differentiation trajectory, CD4 T cell helper function, T cell contributions to immunotherapy and autoimmune pathogenesis. We also discuss the development and function of γδ T cells in tissue surveillance, infection, and tumor immunity. Finally, we summarized current T-cell-based immunotherapies in both cancer and autoimmune diseases, with an emphasis on their clinical applications. A better understanding of T cell immunity provides insight into developing novel prophylactic and therapeutic strategies in human diseases.
T 细胞对于维持健康和预防疾病的免疫功能至关重要。T 细胞发育是在胸腺中逐步进行的，主要产生 CD4 和 CD8 T 细胞亚群。抗原刺激后，幼稚 T 细胞分化为 CD4 辅助和 CD8 细胞毒性效应和记忆细胞，介导直接杀伤、多种免疫调节功能和长期保护。针对急性和慢性感染及肿瘤，T 细胞采用不同的分化轨迹，在转录和表观遗传程序的精确和精心调控下，发展为具有不同表型、分化潜能和功能的各种异质性群体。异常 T 细胞免疫可引发并促进自身免疫病的发病机制。在本综述中，我们总结了 T 细胞发育、CD4 和 CD8 T 细胞分类以及生理状态下分化的最新认识。我们进一步阐述了 CD4 和 CD8 T 细胞在传染病、慢性感染和肿瘤以及自身免疫病中的异质性、分化、功能和调控网络，强调了耗竭的 CD8 T 细胞分化轨迹、CD4 T 细胞辅助功能、T 细胞在免疫治疗和自身免疫发病机制中的作用。我们还讨论了 γδ T 细胞在组织监视、感染和肿瘤免疫中的发育和功能。最后，我们总结了目前癌症和自身免疫病中的 T 细胞为基础的免疫疗法，重点介绍了它们的临床应用。对 T 细胞免疫的深入了解为开发人类疾病的新型预防和治疗策略提供了思路。
