The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection.
The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection.
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DOI：
10.3389/fimmu.2016.00093
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发表时间：
2016
影响因子：
7.3
通讯作者：
Workman AM
中科院分区：
文献类型：
--
作者：
Brown DM;Lampe AT;Workman AM
在第二类MHC背景下识别多肽抗原的CD4T细胞可以分化为具有辅助功能的各种亚群。然而，越来越多的证据表明，具有直接细胞溶解活性(CD4CTL)的CD4细胞在慢性和急性感染中发挥作用，如甲型流感病毒(IAV)感染。在过去的几十年里，测量这些细胞的频率和活性的技术已经证明，它们在感染中含量丰富，如人类免疫缺陷病毒、鼠痘、小鼠伽玛疱疹病毒、巨细胞病毒、爱泼斯坦-巴尔病毒和流感等。我们现在认识到，CD4CTL作为病毒感染和抗肿瘤免疫的直接效应者，通过获得穿孔素介导的细胞溶解活性和对病毒感染靶点或肿瘤的溶解做出贡献，在病毒感染和抗肿瘤免疫中发挥更大的作用。早在20世纪80年代，在流感病毒感染后，人们就发现了具有细胞溶解能力的CD4T细胞克隆，但这一早期工作大多依赖于体外培养，对CD4CTL的生理相关性知之甚少。在这里，我们讨论了CD4CTL在预防致死性IAV感染中的直接作用，以及在IAV感染过程中体内CD4细胞产生穿孔素介导的裂解活性的因素。在专注于IAV感染过程中产生的CD4CTL的同时，我们从其他抗病毒和抗肿瘤系统的文献中进行比较。此外，我们重点介绍了目前已知的关于CD4CTL次级和记忆反应的情况，以及诱导这些强大的杀伤细胞的疫苗接种策略，这些细胞提供了一层额外的细胞介导的免疫保护，以抵御异型IAV感染。
CD4 T cells that recognize peptide antigen in the context of class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL) play a role in chronic as well as acute infections, such as influenza A virus (IAV) infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections, such as human immunodeficiency virus, mouse pox, murine gamma herpes virus, cytomegalovirus, Epstein–Barr virus, and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and antitumor immunity through their ability to acquire perforin-mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin-mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other antiviral and antitumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell-mediated immune protection against heterosubtypic IAV infection.