BASIC AND CLINICAL STUDIES OF THE HUMAN C3B RECEPTOR

人类 C3B 受体的基础和临床研究

• 批准号: 3446271
• 负责人: James Graham Wilson
• 金额: $ 6.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3446271
• 关键词: T lymphocyte; cell mediated cytotoxicity; child (0-11); flow cytometry; genetic regulation; helper T lymphocyte; human subject; immunogenetics; juvenile rheumatoid arthritis; monoclonal antibody; monocyte; neutrophil; orphan disease /drug; rheumatoid arthritis; scleroderma; suppressor T lymphocyte; systemic lupus erythematosus; tissue /cell culture

It has recently been demonstrated that patients with systemic lupus erythematosus have a decreased number of C3B receptors on their erythrocytes. This trait is genetically determined and thus precedes and may predispose to the development of disease. It is not known how decreased erythrocyte C3b receptors participate in the pathogenesis of lupus, whether other cell types also have decreased C3b receptors, or whether inflammatory diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, and scleroderma are also associated with abnormalities of C3b receptors. Studies enumerating cellular C3b receptors by immunofluorescent flow cytometry and radioligand binding will be extended to polymorphonuclear leukocytes, monocytes, and lymphocytes to determine whether genetic control of C3b receptor number affects multiple cell types, and will focus on patients with a variety of manifestations of lupus and other inflammatory diseases, to learn how abnormalities of C3b receptors may affect the expression of inflammatory processes. Contrary to the conclusions of earlier studies, it now has been shown that a proportion of T lymphocytes have C3b receptor antigen and are able to form rosettes with bovine erythrocytes bearing C3b (Eb-C3b). It has not been established whether these T cells reside within a previously identified subset, nor have their functional capacities been determined. T cells which have C3b receptors will be purified based on their ability to form rosettes with Eb-C3b and by fluorescence-activated sorting techniques, and will be characterized according to their reactivity with monoclonal antibodies, the presence or absence on their surface of receptors for immunoglobulins, their response to mitogens, and their function in assays for helper, suppressor, natural killer, and antibody-dependent cytotoxic activities.

最近的研究表明，系统性狼疮患者 红斑狼疮患者的 C3B 受体数量减少 红细胞。 该特征是由基因决定的，因此先于并且 可能会诱发疾病的发展。 不知道如何 红细胞C3b受体减少参与了发病机制 狼疮，其他细胞类型是否也有 C3b 受体减少，或 是否患有炎症性疾病，如类风湿性关节炎、青少年 类风湿性关节炎、硬皮病也与 C3b受体异常。 细胞 C3b 受体研究 通过免疫荧光流式细胞术和放射性配体结合将 扩展到多形核白细胞、单核细胞和淋巴细胞 确定 C3b 受体数量的遗传控制是否影响多个 细胞类型，并将重点关注具有多种表现的患者 狼疮和其他炎症性疾病，了解 C3b 异常如何 受体可能影响炎症过程的表达。 与此相反 根据早期研究的结论，现在已经表明，有一部分 的 T 淋巴细胞具有 C3b 受体抗原并能够形成玫瑰花结 牛红细胞带有 C3b (Eb-C3b)。 尚未成立 这些 T 细胞是否位于先前识别的子集中，也 他们的功能能力已经确定。 具有 C3b 的 T 细胞 受体将根据其形成玫瑰花结的能力进行纯化 Eb-C3b 并通过荧光激活分选技术，并将 根据与单克隆抗体的反应性进行表征， 其表面存在或不存在免疫球蛋白受体， 他们对有丝分裂原的反应，以及他们在辅助分析中的功能， 抑制、自然杀伤和抗体依赖性细胞毒活性。