PROPERTIES OF DENDRITIC CELLS AND MACROPHAGES

树突状细胞和巨噬细胞的特性

• 批准号: 3480716
• 负责人: Ralph Marvin Steinman
• 金额: $ 29.15万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480716
• 关键词: Langerhans' cell; T lymphocyte; antibody formation; antimitotics; clone cells; dendrites; helper T lymphocyte; histocompatibility antigens; hybridomas; laboratory mouse; laboratory rabbit; laboratory rat; leukocyte activation /transformation; lymphatic tissue; lymphokines; macrophage; phagocytosis; scanning electron microscopy

The grant will study several cell types that are important in the generation of immune responses: dendritic cells, which are active stimulators of cell-mediated immunity, particularly transplant rejection; macrophages, which are capable of resisting microorganisms and tumors; and helper T lymphocytes, which promote many host defense mechanisms such as antibody formation and killer T cells. The work is divided into 4 subprojects, each in progress and each carried out by specific personnel. The projects require the isolation and characterization of defined murine cell types in culture. A. Skin dendritic cells (Langerhans cells) are immunologically immature, but become active accessory cells in culture. Monoclonal antibodies (MAb) will be raised to immature and mature Langerhans cells to help identify functionally significant, dendritic cell surface molecules, and to localize analogous cells in tissues other than skin. B. Leukocytes will be isolated from the livers of mice that are resisting infection with Listeria. The cells will be used to determine the types of T lymphocytes, antigens, and lymphokines that sustain the microbicidal activities of macrophages derived from an inflammatory site. C. Surface molecules involved in the interaction of dendritic cells and responding lymphocytes will be studied in discrete cell aggregates which form during immune responses in culture. ImmunoEM with MAb will localize specific proteins at dendritic-T cell contact zones. MAb will be tested as blockers of clustering and of function within aggregates. Mediators required for the early stage of T cell activation will be studied with emphasis on factors and bioassays that explain the capacity of dendritic cells to make helper lymphocytes IL-2 responsive. D. The function of helper T lymphocytes will be analyzed with a new model in which the cells are primed to carrier proteins in culture. The relative capacity of helper cells to respond to native vs. degraded proteins will be documented. The different requirements for the growth and differentiation of hapten-specific B lymphocytes will be considered with intact, carrier-specific T cells as helper cells. The function of interleukins and dendritic cells in the development of killer T cells, which like antibody secreting cells require helper lymphocytes, will be studied using unprimed lyt-2 T cells as responders.

该基金将研究几种细胞类型，这些细胞类型在人类免疫系统中很重要。 产生免疫反应：树突状细胞，这是积极的 细胞介导的免疫刺激剂，特别是移植排斥; 巨噬细胞，其能够抵抗微生物和肿瘤;以及 辅助性T淋巴细胞，促进许多宿主防御机制， 抗体形成和杀伤T细胞。 这项工作分为4个分项目，每个分项目正在进行，每个分项目已完成 由特定的人员。 这些项目需要隔离， 在培养物中确定的鼠细胞类型的表征。 A.皮肤树突状细胞（朗格汉斯细胞）在免疫学上是不成熟的， 但在培养中成为活跃的辅助细胞。 单克隆抗体（MAb） 将被培养成未成熟和成熟的朗格汉斯细胞， 功能显著的树突状细胞表面分子，并定位 皮肤以外的组织中的类似细胞。 B。白细胞将从抵抗的小鼠肝脏中分离出来， 李斯特菌感染 这些细胞将用于确定 T淋巴细胞、抗原和淋巴因子，它们维持杀微生物剂 来自炎症部位的巨噬细胞的活性。 C.参与树突状细胞和树突状细胞相互作用的表面分子 将在离散的细胞聚集体中研究应答淋巴细胞， 在培养的免疫反应中形成。 单克隆抗体免疫电镜将定位 树突状T细胞接触区的特异性蛋白质。 MAb将进行测试， 聚集和聚集体内功能的阻滞剂。 调解员 T细胞活化的早期阶段所需的将被研究， 强调解释树突状细胞能力的因素和生物测定， 细胞，使辅助淋巴细胞IL-2反应。 D.辅助性T淋巴细胞的功能将用一种新的模型进行分析 其中细胞在培养物中被致敏于载体蛋白。 的相对 辅助细胞对天然蛋白质与降解蛋白质的反应能力将是 记录在案。 对生长和分化的不同要求 半抗原特异性B淋巴细胞的数量将被视为完整， 载体特异性T细胞作为辅助细胞。 白细胞介素的功能和 树突状细胞在杀伤性T细胞的发展中， 分泌细胞需要辅助淋巴细胞，将使用未引发的 lyt-2 T细胞作为应答者。