M CELL UPTAKE AND CYTOARCHITECTURE IN PEYER'S PATCHES

本项目的长期目标是调节M 细胞并转运至肠淋巴器官中的淋巴细胞。 的 用粘附于M细胞的探针靶向M细胞的能力将是 在小鼠和兔动物模型中研究。 运送老鼠 将针对兔M细胞表面的单克隆抗体与 不与M细胞表面结合的单克隆抗体。 由于这些 小鼠单克隆抗体也是兔的外源蛋白， 将研究粘膜分泌物中的抗原特异性伊加，以确定 结合是否会增强粘膜免疫应答的产生。 结合M细胞的凝集素将被用作增强抗原的载体， 通过M细胞的摄取和随后的伊加免疫应答的发展。 的 将在体内检查调节M细胞摄取颗粒的能力 通过使用与M共轭的两种不同颜色的荧光微球 细胞结合凝集素。 M细胞被伽马射线刺激后， 表达细胞表面Ia的干扰素将被抗Ia抗原靶向 共轭 M细胞对抗原的摄取对T细胞活化的影响 将定义粘膜T细胞。 将测定T细胞的活化 通过检测粘膜T细胞上的T细胞活化分子， T细胞系。 M细胞在体内传递激活信号的能力 将在有丝分裂原与M细胞表面结合后进行检查。 的能力 将在体外评估活化的T细胞选择性结合M细胞 以确定淋巴细胞浸润M细胞的相关因素。 了解M细胞对抗原和颗粒的摄取与以下因素有关： 优化口服免疫，对抗肠道感染， 阐明粘膜免疫疾病的发病机制。

The long term objective of this project is to regulate antigen uptake by M cells and transport to lymphoid cells in intestinal lymphoid organs. The ability to target M cells with probes adherent to M cells will be investigated in mouse and rabbit animal models. Transport of a mouse monoclonal antibody against the rabbit M cell surface will be compared to a monoclonal antibody that does not bind to M cell surfaces. Since these mouse monoclonal antibodies are also foreign proteins to rabbits, levels of antigen specific IgA in mucosal secretions will be studied to determine whether binding will enhance generation of a mucosal immune response. Lectins which bind to M cells will be used as vectors to enhance antigen uptake by M cells and development of a subsequent IgA immune response. The ability to regulate uptake of particles by M cells will be examined in vivo by using fluorescent microspheres of two different colors conjugated to M cell binding lectins. M cells which have been stimulated by gamma- interferon to express cell surface la will be targeted with anti-la:antigen conjugates. The effect of antigen uptake by M cells on the activation of mucosal T cells will be defined. Activation of T cells will be determined by detection of a T cell activation molecule on mucosal T cells and rabbit T cell lines. The ability of M cells to convey activation signals in vivo will be examined after mitogen binding to M cell surfaces. The capacity of activated T cells to selectively bind to M cells will be assessed in vitro to determine factors involved in infiltration of M cells by lymphocytes. Understanding M cell uptake of antigens and particles is relevant for optimizing oral immunization, combating intestinal infection, and delineating the pathogenesis of mucosal immunologic diseases.