CD8 NK/T Cells and the Phylogeny of Cellular Immunity

CD8 NK/T 细胞和细胞免疫的系统发育

• 批准号: 0136536
• 负责人: Jacques Robert
• 金额: $ 52.53万
• 依托单位: University of Rochester
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0136536&HistoricalAwards=false
• 关键词: CD8; NK; Cells; Phylogeny; Cellular

CD8 cytotoxic T-lymphocytes (CTL) recognize and kill targets that express antigenic peptides in the context of major histocompatibility complex (MHC) class I molecules. As such, CTL are crucially involved in the generation of adaptive immunity against viruses and tumors. Natural killer (NK) cells play an active role in innate immunity by detecting and killing virally-infected or tumor cells that have down-regulated their surface MHC class I molecules thereby escaping surveillance by the adaptive immune system. Growing evidence suggests that some immune responses are mediated by CTL expressing NK-associated molecules (CD8/NK T-cells). The biology and physiological significance of the complexity and heterogeneity of NK-associated molecules and their expression by different effectors (e.g. CTL) is unclear. Since it is now well established in several species, including frogs, that certain heat shock proteins (e.g. gp96 or hsp70) elicit both adaptive CD8 T-cell mediated responses against the antigenic peptides they chaperone, and innate immune responses, it will be of significance to explore, for the first time, the extent to which this putative ancestral system of hsp-generated immunity may involve CTL that express NK-associated molecules. In addition, an unequivocal characterization of NK/T-cells in an amphibian that occupies a pivotal position in the evolution of vertebrates would support the hypothesis that CD8 NK/T-cells represent an important evolutionary step that bridges the innate and adaptive immune systems. This finding would also attest of the importance of this cell type in immunity of mammals. Finally, a better knowledge of cell-mediated cytotoxicity in Xenopus may have crucial implication with respect to understanding putative defects in the immune defense systems used against those viral pathogens that are causing world-wide declines of amphibian populations. The overall goal of this project is to take advantage of our Xenopus model to assess, from an evolutionary perspective, the role of CD8 NK/T cells, both in vitro and in vivo, in innate and adaptive immune responses to tumor, viral, and minor histocompatibility antigens as well as to explore the idea that T-cells co-expressing CD8 and NK markers (CD8 NK/T-cells) are phylogenetically early mediators of cellular immunity. Natural killer and cytotoxic T-lymphocytes are two important types of immune cells involved in defense against virus infections and tumor. Recent studies suggest the existence of a novel cell type with intermediate characteristics. The goal of the research program is to use the frog Xenopus rather than mice as a model system to better understand the role of this new type of immune cell in immune defense against cancer and virus infections from an evolutionary perspective.

CD8细胞毒性T淋巴细胞（CTL）识别并杀死在主要组织相容性复合物（MHC）I类分子的背景下表达抗原肽的靶标。 因此，CTL与病毒和肿瘤的适应性免疫产生至关重要。 天然杀伤（NK）细胞通过检测和杀死降低其表面MHC I类分子的病毒感染或肿瘤细胞而在先天免疫中起积极作用，从而通过适应性免疫系统逃避了监视。越来越多的证据表明，某些免疫反应是由表达NK相关分子（CD8/NK T细胞）的CTL介导的。 NK相关分子的复杂性和异质性的生物学和生理意义及其通过不同效应子（例如CTL）的表达尚不清楚。由于现在已经在包括青蛙在内的几种物种中建立了很好的确定，因此某些热休克蛋白（例如GP96或HSP70）引起了对它们伴侣的抗原肽的适应性CD8 T细胞介导的反应，以及先天性免疫反应，这将是首次涉及该系统的范围，这将是涉及该系统的范围，这将具有重要意义。 NK相关的分子。此外，在两栖动物中NK/T细胞的明确表征在脊椎动物的演化中占据关键位置将支持以下假设：CD8 NK/T细胞代表了重要的进化步骤，它弥合了先天和适应性免疫系统。这一发现还将证明这种细胞类型在哺乳动物免疫中的重要性。 最后，对爪蟾中细胞介导的细胞毒性的更好知识可能对理解用于理解的免疫防御系统中的假定缺陷具有至关重要的意义，用于针对那些在全球范围内减少两栖动物种群下降的病毒病原体。 该项目的总体目的是利用我们的武士模型从进化的角度评估CD8 NK/T细胞在体外和体内的作用，在天生和适应性免疫反应中对肿瘤，病毒性和次要的组织抗原性的反应，以及探索T-Cells COD/nk的想法，以探索CD8 NK的想法。细胞免疫的系统发育早期介质。天然杀伤和细胞毒性T淋巴细胞是参与防御病毒感染和肿瘤的两种重要类型的免疫细胞。最近的研究表明存在具有中间特征的新细胞类型。 研究计划的目的是使用青蛙爪蟾，而不是小鼠作为模型系统，以更好地了解这种新型免疫细胞在免疫防御癌症和病毒感染中的作用。