M CELL UPTAKE AND CYTOARCHITECTURE IN PEYER'S PATCHES

我们的目标是界定以下机构的职能和规管 肠淋巴器官 这些目标与口腔相关 免疫、肠道感染、抗原的M细胞摄取和 颗粒，包括HTLV III，以及免疫性 疾病 第一个具体目标是界定对生物体的吸收和转运， 微粒微生物抗原、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的运输机制， 淋巴组织 衣原体感染的后果 淋巴滤泡增生对M细胞增殖和 将评价管腔颗粒的摄取。 调制 分泌伊加从肠腔中摄取抗原， 使用霍乱弧菌以及带有和的微球进行评估 没有伊加抗体。 含有3 H标记蛋白质的脂质体或 胶体金颗粒将用于评价经口给药 抗原和药物通过M细胞。 迁移途径 将追踪单核白细胞以确定细胞是否 可以携带肠腔中的抗原进入派尔集合淋巴结。 第二个具体目标是研究Peyer's的调制 通过抗原刺激的细胞结构和功能， 通过消耗正常小鼠中的调节性淋巴细胞亚群， 在系统性红斑狼疮（SLE）小鼠模型中。 的 肠道抗原刺激调节 将评价派尔集合淋巴结中的表面IG同种型转换 通过免疫标记和荧光激活细胞分选（FACS）。 将使用单克隆抗体耗竭淋巴细胞亚群; 免疫调节细胞的后续变化对免疫调节细胞的影响。 粘膜淋巴器官的细胞结构将通过 在正常小鼠和自身免疫小鼠中的免疫标记， 辅助性T细胞耗竭治疗SLE。

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.