CD4 CTL, a Cytotoxic Subset of CD4(+) T Cells, Their Differentiation and Function.
CD4 CTL, a Cytotoxic Subset of CD4(+) T Cells, Their Differentiation and Function.
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DOI：
10.3389/fimmu.2017.00194
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发表时间：
2017
影响因子：
7.3
通讯作者：
Saito T
中科院分区：
文献类型：
--
作者：
Takeuchi A;Saito T
在各种免疫反应中都观察到具有细胞毒活性的 CD4+ T 细胞 (CD4 CTL)。这些细胞的特点是能够分泌颗粒酶 B 和穿孔素，并以 MHC II 类限制的方式杀死靶细胞。尽管 CD4 CTL 曾经被认为是与长期培养相关的体外产物，但后来它们在体内得到了鉴定，并被证明在抗病毒和抗肿瘤免疫以及炎症中发挥着重要作用。 CD4 CTL 的功能特征表明它们对于治疗目的具有潜在意义。然而，为了开发有效的 CD4 CTL 疗法，有必要了解这些细胞的分化和生成。尽管调节各种 CD4+ Th 亚群发育的机制已在细胞因子和转录因子需求方面得到阐明，但 CD4 CTL 分化机制仍然难以捉摸。这些细胞被认为与分泌 IFNγ 的 Th1 细胞关系最密切，并受脱中胚层蛋白和/或 T-bet 转录因子的调节而分化。然而，我们和其他人的研究已经在其他 CD4+ T 细胞亚群（包括初始 T 细胞）中鉴定出 CD4 CTL。我们已经鉴定出 I 类限制性 T 细胞相关分子作为 CD4 CTL 的标记，并且通过使用该标记，我们检测到了具有分化为 CD4 CTL 潜力的幼稚 T 细胞子集。 CD4 CTL 在感染和炎症部位形成。在这篇综述中，我们总结了有关 CD4 CTL 生成的最新发现，并提出了一个具有多种分化途径的模型。
CD4+ T cells with cytotoxic activity (CD4 CTL) have been observed in various immune responses. These cells are characterized by their ability to secrete granzyme B and perforin and to kill the target cells in an MHC class II-restricted fashion. Although CD4 CTLs were once thought to be an in vitro artifact associated with long-term culturing, they have since been identified in vivo and shown to play important roles in antiviral and antitumor immunity, as well as in inflammation. Functional characterization of CD4 CTL suggests their potential significance for therapeutic purposes. However, in order to develop effective CD4 CTL therapy it is necessary to understand the differentiation and generation of these cells. Although the mechanisms regulating development of various CD4+ Th subsets have been clarified in terms of the cytokine and transcription factor requirement, the CD4 CTL differentiation mechanism remains elusive. These cells are thought to be most closely related to Th1 cells secreting IFNγ and regulated by eomesodermin and/or T-bet transcription factors for their differentiation. However, our studies and those of others have identified CD4 CTLs within other CD4+ T cell subsets, including naïve T cells. We have identified class I-restricted T cell-associated molecule as a marker of CD4 CTL and, by using this marker, we detected a subset of naïve T cells that have the potential to differentiate into CD4 CTL. CD4 CTL develops at sites of infections as well as inflammation. In this review, we summarize recent findings about the generation of CD4 CTL and propose a model with several differentiation pathways.