ALVEOLAR MACROPHAGES IN FIV INFECTION

描述：（改编自应用程序）关键是一个更好的 了解艾滋病毒相关肺部疾病的发病机制是一个 与HIV相关免疫缺陷相似的动物慢病毒模型。 有证据表明，导致猫艾滋病的慢病毒，猫 免疫缺陷病毒（FIV）导致严重的肺部免疫缺陷 其特征在于对弓形虫肺炎的易感性增加。 拟议的研究将采用FIV检查缺陷 肺泡巨噬细胞（AM）功能。 该申请描述了实验 旨在检验两个假设：第一， HIV/FIV患者AM的激活是病毒感染的直接结果 AM独立于淋巴因子调节;其次，HIV/FIV 感染会抑制自分泌干扰素（IFN）-γ环， 用于IL-12产生的主要AM。 a.职业发展计划：该计划包括两个阶段。 期间 第一阶段里奇博士将完成博士学位训练 他进入 博士计划于1993年7月，并已完成教学培训， 以及初步检查。 在第二阶段（第三和第四年）， 博士里奇将留在北卡罗来纳州州立大学， 博士后职位 B.研究计划：猫免疫缺陷病毒（FIV）将用于 检查肺泡巨噬细胞（AM）功能的缺陷。 实验 计划测试两个假设：第一， HIV/FIV患者AM的激活是病毒感染的直接结果 AM独立于淋巴因子调节;其次，HIV/FIV 感染抑制了启动AM所必需的自分泌IFN-γ环， IL-12产生。 该计划前三年的研究将 通过评估AM的细胞因子表达模式来验证这些假设 在体内FIV感染后以时间方式收集。 最后一 一年的研究将把体外研究的结果 用T.刚地。

DESCRIPTION: (Adapted from the application) Critical to a better understanding of the pathogenesis of HIV-associated lung disease is an animal lentivirus model that parallels HIV-associated immunodeficiency. Evidence suggests that the feline AIDS-causing lentivirus, Feline Immunodeficiency Virus (FIV) causes serious pulmonary immunodeficiency characterized by increased susceptibility to Toxoplasma gondii pneumonia. The proposed research will employ the use of FIV for examining the defects in alveolar macrophage (AM) function. The application describes experiments designed to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine interferon (IFN)-gamma loop necessary to prime AM for IL-12 production. a. Career Development Plan: The plan consists of two phases. During the first Phase, Dr. Ritchey will complete his Ph.D. training. He entered the Ph.D. program in July of 1993, and has completed the didactic training as well as the preliminary examination. In phase two (years three and four), Dr. Ritchey will remain at North Carolina State University, in a postdoctoral position. b. Research Plan: Feline Immunodeficiency Virus (FIV) will be used to examine the defects in alveolar macrophage (AM) function. Experiments are planned to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine IFN-gamma loop necessary to prime AM for IL-12 production. Studies during the first three years of this program will test these hypotheses by evaluating cytokine expression patterns of AM collected in a temporal fashion following in vivo FIV infection. The last year of this research will correlate the results of the in vitro studies with in vivo challenge of FIV-infected cats with T. gondii.