MECHANISMS WHEREBY CD4 T CELLS ACTIVATE AMI AND CMI

CD4 T 细胞激活 AMI 和 CMI 的机制

• 批准号: 2887355
• 负责人: HENRI C VAN DER HEYDE
• 金额: $ 22万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887355
• 关键词: B lymphocyte; Plasmodium; SCID mouse; affinity chromatography; cell mediated cytotoxicity; cellular immunity; enzyme linked immunosorbent assay; flow cytometry; fluorescence microscopy; gas chromatography; genetically modified animals; helper T lymphocyte; humoral immunity; immunoregulation; interferon gamma; interleukin 10; interleukin 2; interleukin 4; laboratory mouse; leukocyte activation /transformation; macrophage; malaria; monoclonal antibody; polymerase chain reaction; western blottings

Despite many years of intensive effort to conquer malaria, it remains a leading cause of death due to an infectious disease. The recent advent of drug-resistant malarial parasites and the development of insecticide resistance by the mosquito vector jointly make the development of immune-based therapy or prophylaxis highly desirable. To do so, requires a detailed understanding of the immune response to malarial antigens. CD4+ T cells are believed to be essential for the resolution of bloodstage malaria (the stage examined in this proposal), but little is known about how CD4+ T cells actually influence protective effector mechanisms. Resolution of acute infections caused by different rodent species of Plasmodium appear to use distinct mechanisms of resolution, with P. yoelii being suppressed by antibody-mediated immunity (AMI) and P. chabaudi by cell-mediated immunity. Our goal is to use these species of Plasmodium to elucidate the molecular mechanisms whereby CD4+ T cells, by differentiating into distinct Th cell-phenotypes, regulate B cell and macrophage function during malaria. To address this goal, we intend to first examine in detail Th cell-differentiation and its requirement for resolution of infection. These findings will be incorporated into subsequent studies aimed at identifying how Th cell- differentiation affects selected parameters of protective antibody development and macrophage function during malaria. We will also address the question of whether antibodies augment macrophage function in vivo to clear parasites from blood. The results of these studies will aid in the design of future experiments crucial to our understanding of protective immune mechanisms responsible for the resolution of malaria in humans.

尽管多年来为战胜疟疾付出了巨大的努力，但它仍然是一个 传染病导致死亡的主要原因。最近的出现 耐药性疟疾寄生虫的研究与杀虫剂的开发 蚊媒的抵抗力共同促进了 非常需要基于免疫的治疗或预防。为此，需要 详细了解对疟疾抗原的免疫反应。 CD4+ T 细胞被认为对于解决以下问题至关重要 血期疟疾（本提案中检查的阶段），但很少有 了解 CD4+ T 细胞实际上如何影响保护性效应器 机制。解决不同啮齿动物引起的急性感染 疟原虫种类似乎使用不同的解决机制， P. yoelii 被抗体介导的免疫 (AMI) 抑制，并且 P. chabaudi 通过细胞介导的免疫。我们的目标是利用这些物种 疟原虫的研究阐明了 CD4+ T 的分子机制 细胞通过分化成不同的 Th 细胞表型，调节 B 疟疾期间细胞和巨噬细胞的功能。为了实现这一目标，我们 打算首先详细检查 Th 细胞分化及其 解决感染的要求。这些发现将 纳入后续研究，旨在确定 Th 细胞如何 分化影响保护性抗体的选定参数 疟疾期间的发育和巨噬细胞功能。我们还将针对 抗体是否增强体内巨噬细胞功能的问题 清除血液中的寄生虫。这些研究的结果将有助于 未来实验的设计对于我们的理解至关重要 负责解决疟疾的保护性免疫机制 在人类中。