MECHANISMS WHEREBY CD4 T CELLS ACTIVATE AMI AND CMI

CD4 T 细胞激活 AMI 和 CMI 的机制

• 批准号: 6169768
• 负责人: HENRI C VAN DER HEYDE
• 金额: $ 19.46万
• 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/6169768
• 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.

尽管多年来征服疟疾的强化努力，但它仍然是 由于传染病引起的主要死亡原因。最近的降临 耐药疟原虫和杀虫剂的发展 蚊子载体的抵抗共同使 高度可取的基于免疫的治疗或预防。为此，需要 对疟疾抗原的免疫反应的详细理解。 CD4+ T细胞被认为对于分辨率至关重要 血阶段的疟疾（该提案中检查的阶段），但几乎没有 知道CD4+ T细胞如何实际影响保护效应器 机制。由不同的啮齿动物引起的急性感染的分辨率 疟原虫似乎使用了不同的分辨率机制， 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力。我们的目标是使用这些物种 疟原虫以阐明CD4+ T的分子机制 细胞通过区分不同的TH细胞表型，调节B 疟疾期间的细胞和巨噬细胞功能。为了解决这个目标，我们 打算首先详细检查细胞分化及其 需要解决感染的要求。这些发现将是 纳入随后的研究，旨在确定细胞 分化会影响保护抗体的选定参数 疟疾期间的发育和巨噬细胞功能。我们还将解决 抗体是否增加体内巨噬细胞功能的问题 从血液中清除寄生虫。这些研究的结果将有助于 未来实验的设计对我们对理解至关重要 保护疟疾的保护性免疫机制 在人类中。