美国休斯顿卫理公会医院Wenhao Chen研究团队探明，CD4+ T细胞免疫依赖于一个内在的干细胞样程序。相关论文于2024年1月2日发表在《自然—免疫学》杂志上。

他们确定了一个干细胞样程序，控制移植模型中的CD4+ T细胞反应。单细胞转录组学分析显示，移植受者的幼稚异体抗原特异性CD4+ T细胞发育为TCF1hi效应前体(TEP)细胞和TCF1−CXCR6+效应细胞。TCF1−CXCR6+CD4+效应体在过继转移到次级宿主后失去增殖能力，并且不排斥同种异体移植物。相比之下，TCF1hiCD4+ TEP细胞具有自我更新和效应分化潜能的双重特征，异体移植物排斥反应依赖于TCF1hiCD4+ TEP细胞中TCF1−CXCR6+效应物的持续补充。

机制上，TCF1维持CD4+ TEP细胞群，而转录因子IRF4和糖酵解酶LDHA控制CD4+ TEP细胞的效应分化潜能。T细胞中IRF4或LDHA的缺失诱导移植接受。这些发现揭示了一个控制CD4+ TEP细胞自我更新能力和效应分化潜力的干细胞样程序，并对T细胞相关免疫治疗具有启示意义。

据介绍，CD4+ T细胞是各种免疫反应的核心，但驱动和维持CD4+ T细胞免疫的分子程序并不完全清楚。

附：英文原文

Title: CD4+ T cell immunity is dependent on an intrinsic stem-like program

Author: Zou, Dawei, Yin, Zheng, Yi, Stephanie G., Wang, Guohua, Guo, Yang, Xiao, Xiang, Li, Shuang, Zhang, Xiaolong, Gonzalez, Nancy M., Minze, Laurie J., Wang, Lin, Wong, Stephen T. C., Osama Gaber, A., Ghobrial, Rafik M., Li, Xian C., Chen, Wenhao

Issue&Volume: 2024-01-02

Abstract: CD4+ T cells are central to various immune responses, but the molecular programs that drive and maintain CD4+ T cell immunity are not entirely clear. Here we identify a stem-like program that governs the CD4+ T cell response in transplantation models. Single-cell-transcriptomic analysis revealed that naive alloantigen-specific CD4+ T cells develop into TCF1hi effector precursor (TEP) cells and TCF1CXCR6+ effectors in transplant recipients. The TCF1CXCR6+CD4+ effectors lose proliferation capacity and do not reject allografts upon adoptive transfer into secondary hosts. By contrast, the TCF1hiCD4+ TEP cells have dual features of self-renewal and effector differentiation potential, and allograft rejection depends on continuous replenishment of TCF1CXCR6+ effectors from TCF1hiCD4+ TEP cells. Mechanistically, TCF1 sustains the CD4+ TEP cell population, whereas the transcription factor IRF4 and the glycolytic enzyme LDHA govern the effector differentiation potential of CD4+ TEP cells. Deletion of IRF4 or LDHA in T cells induces transplant acceptance. These findings unravel a stem-like program that controls the self-renewal capacity and effector differentiation potential of CD4+ TEP cells and have implications for T cell-related immunotherapies.

DOI: 10.1038/s41590-023-01682-z

Source: https://www.nature.com/articles/s41590-023-01682-z