MECHANISMS WHEREBY CD4 T CELLS ACTIVATE AMI AND CMI

CD4 T 细胞激活 AMI 和 CMI 的机制

• 批准号: 2640738
• 负责人: HENRI C VAN DER HEYDE
• 金额: $ 16.6万
• 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/2640738
• 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.

尽管多年来为征服疟疾作出了大量努力，但它仍然是一个严重的疾病