SPECIFICITY, DISTRIBUTION AND FUNCTION OF GD T CELLS

GD T 细胞的特异性、分布和功能

• 批准号: 2003553
• 负责人: ADRIAN Clive HAYDAY
• 金额: $ 10.06万
• 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/2003553
• 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（改编自研究者摘要）：就目前所知， 所有脊椎动物都含有两种类型的T细胞，α/β和α/β。 γ/δ T细胞，由它们的α/β和γ/δ T细胞区分 抗原受体 α/β T细胞的作用相当好， 这是可以理解的，但γ/δ T细胞的情况并非如此。 研究从 许多研究小组认为，γ/δ T细胞与 α/β T细胞在抗原识别和解剖学方面的作用 本地化 但是，长期以来一直需要生物测定， 以评估γ/δ T细胞和效应子的功能， 在某种程度上，问题是缺乏 γ/δ T细胞，在小鼠和人类中的数量远低于 α/β T细胞。 为了解决这些问题，研究人员的实验室 已经培育出了缺乏α/β T细胞的小鼠，并对它们进行了挑战， 与缺乏γ/δ T细胞的小鼠一起， 寄生虫的目标是肠上皮细胞，一个居住的网站， γ/δ T细胞。 研究人员发现， 小鼠对这种寄生虫的免疫力受到任一基因缺失的显着影响 α/β T细胞或γ/δ T细胞，但以不同的方式。 而 α/β T细胞是保护宿主所必需的，γ/δ T细胞是保护宿主所必需的。 T细胞缺乏与严重的病理学有关。 因此 研究人员认为，α/β和γ/δ T细胞确实 代表了免疫系统的不同组成部分， 因此，对γ/δ T细胞功能的了解对于我们的研究至关重要。 了解免疫相关的病理，特别是肠道，例如， 炎性肠病。 γ/δ T细胞的生物测定提供了 调查员制度应有助于改善这种 认识 将采用细胞和遗传方法。 的 研究者应进行另一项生物测定分析， γ/δ T细胞，研究人员最近开发了 令人信服的证据 在该测定中，γ/δ T细胞提供了显著的生物学效应。 抗微生物保护水平，而不建立免疫力。 一起 这些试验的研究可能揭示为什么γ/δ T细胞如此高， 保守的