M CELL UPTAKE AND CYTOARCHITECTURE IN PEYER'S PATCHES

派伊尔氏斑中的 M 细胞摄取和细胞结构

• 批准号: 3237948
• 负责人: ROBERT LEO OWEN
• 金额: $ 13.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3237948
• 关键词: Chlamydiaceae; Peyer's patches; autoimmune disorder; cholera; colloids; disease /disorder model; gold; human immunodeficiency virus 1; immunoglobulin A; leukocytes; liposomes; lymphatic tissue; tritium

Our objectives are to define the functions and regulation of intestinal lymphoid organs. These goals are relevant to oral immunization, intestinal infection, M cell uptake of antigens and particles, including HTLV III, and to pathogenesis of immunologic diseases. The first specific aim is to define uptake and transport of particulate microbial antigens, tracer particles, and liposomes in animal models. We propose to study the entry route(s) of chlamydia organisms through small intestinal and rectal lymphoid follicle epithelia and the mechanism of transport of these organisms into lymphoid tissues. The consequences of chlamydia-induced hyperplasia of lymphoid follicles on M cell proliferation and uptake of luminal particles will be evaluated. Modulation of antigen uptake from the intestinal lumen by secretory IgA will be assessed using cholera vibrios and also microspheres with and without IgA antibody. Liposomes containing 3H labeled proteins or colloidal gold particles will be used to evaluate peroral delivery of antigens and drugs through M cells. Migration pathways of mononuclear leukocytes will be traced to determine whether cells can carry antigen from the intestinal lumen into Peyer's patches. The second specific aim is to investigate modulation of Peyer's patch cytoarchitecture and function by antigenic stimulation and by depletion of regulatory lymphocyte subsets in normal mice and in a mouse model of systemic lupus erythematosus (SLE). The mechanisms by which intestinal antigen stimulation regulates surface Ig isotype switching in Peyer's patches will be evaluated by immunolabeling and fluorescence activated cell sorting (FACS). Monoclonal antibodies will be used to deplete lymphocyte subsets; the effects of subsequent changes in immunoregulatory cells on the cytoarchitecture of mucosal lymphoid organs will be assessed by immunolabeling in normal mice and in autoimmune mice in which helper T cell depletion treats SLE.

我们的目标是定义以下机构的职能和监管 肠淋巴器官。 这些目标与口语相关 免疫、肠道感染、M细胞摄取抗原和 颗粒，包括 HTLV III，以及免疫学的发病机制 疾病。 第一个具体目标是定义吸收和运输 颗粒微生物抗原、示踪颗粒和脂质体 动物模型。 我们建议研究衣原体的进入途径 微生物通过小肠和直肠淋巴滤泡 上皮细胞和这些生物体转运到的机制 淋巴组织。 衣原体引起的后果 淋巴滤泡增生对M细胞增殖的影响 将评估管腔颗粒的吸收。 调制 分泌型 IgA 从肠腔摄取抗原 使用霍乱弧菌和微球进行评估 没有 IgA 抗体。 含有 3H 标记蛋白质的脂质体或 胶体金颗粒将用于评估口服给药 通过M细胞传递抗原和药物。 的迁移途径 将追踪单核白细胞以确定细胞是否 可以将抗原从肠腔携带到派尔氏集结区。 第二个具体目标是研究 Peyer's 的调制 通过抗原刺激来修补细胞结构和功能 通过消耗正常小鼠的调节性淋巴细胞亚群 在系统性红斑狼疮（SLE）小鼠模型中。 这 肠道抗原刺激调节的机制 将评估派尔氏斑中的表面 Ig 同种型转换 通过免疫标记和荧光激活细胞分选（FACS）。 单克隆抗体将用于消除淋巴细胞亚群； 随后免疫调节细胞的变化对 粘膜淋巴器官的细胞结构将通过以下方式评估 正常小鼠和自身免疫小鼠的免疫标记，其中 辅助 T 细胞耗竭可治疗 SLE。