Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Austria.
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
Immunol Lett. 2022 Jul;247:27-42. doi: 10.1016/j.imlet.2022.05.001. Epub 2022 May 11.
The two major subsets of peripheral T cells are classically divided into the CD4 T helper cells and the cytotoxic CD8 T cell lineage. However, the appearance of some effector CD4 T cell populations displaying cytotoxic activity, in particular during viral infections, has been observed, thus breaking the functional dichotomy of CD4 and CD8 T lymphocytes. The strong association of the appearance of CD4 cytotoxic T lymphocytes (CD4 CTLs) with viral infections suggests an important role of this subset in antiviral immunity by controlling viral replication and infection. Moreover, CD4 CTLs have been linked with anti-tumor activity and might also cause immunopathology in autoimmune diseases. This raises interest into the molecular mechanisms regulating CD4 CTL differentiation, which are poorly understood in comparison to differentiation pathways of other Th subsets. In this review, we provide a brief overview about key features of CD4 CTLs, including their role in viral infections and cancer immunity, and about the link between CD4 CTLs and immune-mediated diseases. Subsequently, we will discuss the current knowledge about transcriptional and epigenetic networks controlling CD4 CTL differentiation and highlight recent data suggesting a role for histone deacetylases in the generation of CD4 CTLs.
外周 T 细胞的两个主要亚群通常被分为 CD4 T 辅助细胞和细胞毒性 CD8 T 细胞谱系。然而，在某些效应 CD4 T 细胞群中观察到了具有细胞毒性活性的出现，特别是在病毒感染期间，这打破了 CD4 和 CD8 T 淋巴细胞的功能二分法。CD4 细胞毒性 T 淋巴细胞（CD4 CTLs）的出现与病毒感染强烈相关，这表明该亚群通过控制病毒复制和感染在抗病毒免疫中具有重要作用。此外，CD4 CTLs 与抗肿瘤活性有关，也可能在自身免疫性疾病中引起免疫病理学。这引起了人们对调节 CD4 CTL 分化的分子机制的兴趣，与其他 Th 细胞亚群的分化途径相比，这些机制还了解甚少。在这篇综述中，我们简要概述了 CD4 CTLs 的关键特征，包括它们在病毒感染和癌症免疫中的作用，以及 CD4 CTLs 与免疫介导的疾病之间的联系。随后，我们将讨论关于控制 CD4 CTL 分化的转录和表观遗传网络的现有知识，并强调最近的数据表明组蛋白去乙酰化酶在 CD4 CTL 的产生中发挥作用。
