IMMUNOREGULATION IN HUMAN SCHISTOSOMIASIS

曼氏血吸虫病实验小鼠模型的特征 迟发性超敏反应细胞对倒伏在 寄主的组织。早期急性胰腺炎所涉及的细胞类型 肉芽肿反应是淋巴细胞(T细胞、B细胞和血浆 巨噬细胞(单核细胞、上皮样细胞和巨细胞) 成纤维细胞、粒细胞(嗜酸性粒细胞、中性粒细胞)和肥大细胞 (1-6)。此外，对小鼠肉芽肿性超敏反应的研究 血吸虫病已证明淋巴细胞亚群在 肉芽肿形成(7、8例)。之前发表的研究使用的是体外试验 肉芽肿模型确立了T细胞亚群在肉芽肿中的作用 肉芽肿中抑制性T细胞途径的形成和鉴定 调制(9，10)。这项提案概述了体外技术，它将 使研究人员能够分析肉芽肿性过敏症 侵入性外科手术给患者带来的风险。一次彻底的 对血吸虫病慢性肉芽肿病的认识 有助于或改善发病率的免疫因素将提供 制定预防方案或 可能减少或改善发病率的临床治疗。其他 研究人员已经确定了在人体内起作用的免疫调节机制 人类血吸虫病。这些机制是用抗原或 丝裂原诱导外周血单核细胞增殖 包括血清因子、黏附性单个核细胞和抑制性T细胞 (11-20)。这项建议旨在检查肉芽肿的形成和 利用体外珠状肉芽肿模型对人类血吸虫病的调节 它概括了迟发性超敏反应的过程 肉芽肿，并提供关于细胞-细胞相互作用的新知识 导致慢性肉芽肿性疾病的发展。目标 这项建议的目的是确定人类T细胞亚群在 肉芽肿的形成和调节，并表征的功能 与诱导者、效应者或抑制者有关的T细胞亚群，并将 免疫调节回路与临床发病程度有关。

Experimental murine models of schistosomiasis mansoni have characterized the delayed type hypersensitivity cellular responses to eggs lodged in the tissues of the host. The cell types involved in the early acute granulomatous responses are lymphocytes (T cells, B cells and plasma cells), macrophages (monocytes, epitheloid cells and giant cells) fibroblasts, granulocytes (eosinophils, neutrophils), and mast cells (1-6). Furthermore, studies of granulomatous hypersensitivity in murine schistosomiasis have demonstrated a role for lymphocyte subsets in granuloma formation (7, 8). Previously published studies using an in vitro granuloma model established a role for T cell subsets in granuloma formation and identified a suppressor T cell pathway in granuloma modulation (9, 10). This proposal outlines in vitro technology which will enable the investigator to analyze granulomatous hypersensitivity without risk to the patient from invasive surgical procedures. A thorough understanding of chronic granulomatous disease in schistosomiasIs and the immunologic factors that contribute to or ameliorate morbidity will provide sound rationale for the development of either prophylactic protocols or clinical treatments that might reduce or ameliorate morbidity. Other investigators have identified immunoregulatory mechanisms operative in human schistosomiasis. These mechanisms were defined using antigen or mitogen induced proliferation of peripheral blood mononuclear cells and include serum factors, adherent mononuclear cells and suppressor T cells (11-20). This proposal intends to examine granuloma formation and modulation in human schistosomiasis, using an in vitro bead granuloma model which recapitulates the process of delayed type hypersensitivity granulomas, and to provide new knowledge of cell-cell interactions which result in the development of chronic granulomatous disease. The objectives of this proposal are to determine the role of human T cell subsets on granuloma formation and modulation, and to characterize the function of the T cell subsets as to inducer, effector or suppressor, and to correlate the immunoregulatory circuits with the degree of clinical morbidity.