SPECIFICITY, DISTRIBUTION AND FUNCTION OF GD T CELLS

GD T 细胞的特异性、分布和功能

• 批准号: 2855975
• 负责人: ADRIAN Clive HAYDAY
• 金额: $ 33.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2855975
• 关键词: T cell receptor; T lymphocyte; bioassay; cell population study; cellular immunity; coccidiosis; gut associated lymphoid tissue; laboratory mouse; leukocyte activation /transformation; microorganism immunology; polymerase chain reaction; protozoa; tissue /cell culture

DESCRIPTION (Adapted from the Investigator's abstract): So far as is known, all vertebrates contain two types of T-cells, an alpha/beta and a gamma/delta T-cell, distinguished by their alpha/beta and gamma/delta T-cell antigen receptors. The role of alpha/beta T-cells is reasonably well understood, but this is not the case for gamma/delta T-cells. Studies from many groups suggest that gamma/delta T-cells are quite different from alpha/beta T-cells in terms of antigen recognition and anatomical localization. But, there has been a longstanding need for a bioassay, by which to assess the function of gamma/delta T-cells and the effector mechanisms(s) that underlie it. In part, the problem has been the scarcity of gamma/delta T-cells, that in mice and humans are much less abundant than alpha/beta T-cells. To tackle these issues, the investigators' laboratory has developed mice that lack alpha/beta T-cells, and have challenged those, together with mice that lack gamma/delta T-cells with a natural protozoan parasite that targets the intestinal epithelium, a resident site of gamma/delta T-cells. The investigators found that the normal response of mice to this parasite is significantly affected by the deletion of either alpha/beta T-cells or gamma/delta T-cells, but in different ways. Whereas alpha/beta T-cells are essential for protection of the host, gamma/delta T-cell deficiency is associated with severe pathology. Thus the investigators believe that alpha/beta and gamma/delta T-cells indeed represent very different components of the immune system, and that an understanding of gamma/delta T-cell functions is therefore essential for our understanding of immune-related pathologies, particularly of the gut, e.g., inflammatory bowel disease. The bioassay for gamma/delta T-cells provided by the investigators' system should facilitate such an improved understanding. Both cellular and genetic approaches will be adopted. The investigators shall undertake the analysis of another bioassay for gamma/delta T-cells, for which the investigators have recently developed convincing evidence. In this assay, gamma/delta T-cells offer a significant level of anti-microbial protection without establishing immunity. Together the study of these assays may reveal why gamma/delta T-cells are so highly conserved.

描述(改编自调查者摘要)：就目前所知， 所有脊椎动物都含有两种类型的T细胞，一种是α/β细胞，另一种是 伽马/德尔塔T细胞，以其α/β和伽马/德尔塔T细胞区分 抗原受体。α/βT细胞的作用相当好 我明白，但伽马/德尔塔T细胞并非如此。研究来自 许多小组认为，伽马/德尔塔T细胞与 抗原识别和解剖学意义上的α/βT细胞 本地化。但是，长期以来，人们一直需要一种生物检测方法，通过 用来评估伽马/德尔塔T细胞和效应器的功能 机制(S)是它的基础。在一定程度上，问题在于稀缺。 在小鼠和人类中，伽马/德尔塔T细胞的含量远远低于 α/βT细胞。为了解决这些问题，调查人员的实验室 已经培育出缺乏α/βT细胞的小鼠，并对这些细胞提出了挑战， 以及缺乏伽马/德尔塔T细胞和天然原虫的小鼠 以肠道上皮为目标的寄生虫，肠道上皮是 伽马/增量T细胞。调查人员发现，患者的正常反应 小鼠对这种寄生虫的感染受到任一基因缺失的显著影响 Alpha/Beta T细胞或Gamma/Delta T细胞，但方式不同。鉴于 α/βT细胞对于保护宿主 T细胞缺乏与严重的病理有关。因此， 研究人员认为，阿尔法/贝塔和伽马/德尔塔T细胞确实 代表着非常不同的免疫系统组成部分，而 因此，了解伽马/德尔塔T细胞功能对于我们的 了解免疫相关的病理，特别是肠道，例如， 炎症性肠病。提供了伽马/德尔塔T细胞的生物测定 由侦查员的系统应该有助于这样的改进 理解。将同时采用细胞和遗传方法。这个 调查人员应承担另一项生物测试的分析工作 伽马/德尔塔T细胞，研究人员最近为其开发了 令人信服的证据。在这项检测中，伽马/德尔塔T细胞提供了显著的 在没有建立免疫力的情况下达到抗微生物保护水平。同舟共济 对这些分析的研究可能会揭示为什么伽马/德尔塔T细胞如此高 保守的。