IMMUNOREGULATION IN DISSEMINATED HISTOPLASMOSIS

本项目的长期目标是研究 免疫调节与病原体感染有关 酵母、荚膜组织胞浆菌（Hc）。 播散性组织胞浆菌病的研究 （D-HPL），将表征可溶性抑制剂和辅助剂 由感染动物的脾细胞产生的因子， 确定它们各自对靶细胞的作用机制。 的 这些因子在体内可能的生物活性也将被 考察 实验性肺组织胞浆菌病的免疫病理学 将在疾病过程中通过免疫组织化学染色进行研究 肉芽肿性炎症中细胞群的连续时间间隔 以及通过支气管肺泡灌洗液（BAL）中细胞的类似染色。 特异性致敏T细胞和未致敏对照T细胞的运输 将测量肉芽肿性炎症部位。 免疫药理学研究将寻求消除抑制细胞活性 如果成功，将确定D-HPL小鼠的生物学特性， 其在宿主对Hc攻击抗性方面的意义。 有待探索的免疫方法包括生产和 向感染的小鼠施用具有活性的单克隆抗体 针对抑制细胞亚群，以及调节细胞内 血管紧张素转化酶在肉芽肿内浸润 抑制剂，卡托普利。 在人类中， 外周血的免疫调节细胞群将通过 流动显微荧光法 调节性细胞亚群的功能特性 外周血将通过体外技术进行研究，包括反向 溶血空斑测定和细胞因子产生测定 特异性和非特异性刺激。 类似的研究将在 细胞获得的BAL患者与肺组织胞浆菌病。

The long-term obejctives of this project are to study the disturbances of immuno-regulation that are associated with infection by the pathogenic yeast, Histoplasma capsulatum (Hc). Studies of disseminated histoplasmosis (D-HPL) in inbred mice, will characterize the soluble suppressor and helper factors that are generated by spleen cells of infected animals and determine their respective mechanism(s) of action on target cells. The possible biological activities of these factors in vivo also will be examined. The immunopathology of experimental pulmonary histoplasmosis will be studied during the disease process by immunohistological staining of cell populations within granulomatous inflammation at serial intervals and by similar staining of cells in bronchoalveolar lavage (BAL) fluid. Traffic of specificity sensitized T cells and unsensitized control T cells to sites of granulomatous inflammation will be measured. Immunopharmacologic studies will seek to abrogate suppressor cell activity in mice with D-HPL and, if successful, will determine the biological significance thereof in respect to host resistance to challenge by Hc. Immunotherapeutic approaches to be explored include the production and the administration to infected mice of monoclonal antibodies with activity against suppressor cell subpopulations and, modulation of the cellular infiltrate within granulomas by the angiotensin converting enzyme inhibitor, captopril. In humans, possible quantitative abnormalities of immunoregulatory cell populations of peripheral blood will be examined by flow microfluorometry. Functional properties of regulatory cell subsets in peripheral blood will be studied by in vitro techniques including reverse hemolytic plaque assay and assays of cytokine production in response to specific and nonspecific stimuli. Similar studies will be performed on cells obtained by BAL patients with pulmonary histoplasmosis.