IMMUNOPATHOGENESIS OF INTESTINAL DISEASE IN AIDS

不明原因的肠道功能障碍在HIV感染者中很常见 不管有没有艾滋病。先前的研究表明，在 HIV抗原和RNA在疾病进展过程中的表达，以及 与组织病理学改变、临床症状和 免疫力改变。在感染艾滋病毒的个体中，这种变化最大。 没有艾滋病。我们假设肠粘膜是首选的 HIV的蓄水池和淋巴细胞感染和感染的场所 被毁了。这一过程是长期的和自我延续的，因为 细菌和其他外来抗原的接近程度以及与改变的 释放调节艾滋病毒复制的细胞因子。然而， 这一过程的致病重要性尚未得到很好的定义。的目标是 这项建议是为了确定艾滋病毒的细胞储存库和含量 检测肠粘膜中的DNA和RNA，以确定粘膜中是否存在HIV RNA 表达与肠道症状、组织病理学有关 改变，加速了疾病的发展。艾滋病病毒的本土化 到细胞损伤的区域将寻求提供直接证据 它在肠道疾病中的作用。研究将涉及艾滋病毒感染者 被跟踪的有症状和无症状的志愿者和对照组 每季度进行一次，并在两年内接受三次GI评估。蜂窝 粘膜和血液中的蓄水池和粘膜病毒含量将 通过RNA原位杂交、DNA和RNA模板特异性检测 聚合酶链式反应、原位聚合酶链式反应、电子和免疫电子 显微镜和免疫组织学。细胞通过凋亡或凋亡进行裂解 将确定明显的合胞体形成和艾滋病毒的存在 通过免疫组织化学和免疫电子显微镜检测。这个 部分细胞因子与特异性抗HIV免疫的相对重要性 将比较和比较在调节粘膜HIV RNA产生方面的功能 推导出了HIV RNA表达的预测模型。演示了 肠粘膜在疾病进展中的重要性可能会导致更好的 了解淋巴系衰竭的潜在机制并可能 导致新的治疗策略。

Unexplained intestinal dysfunction is common in HIV-infected individuals with or without AIDS. Previous studies demonstrated variation in the expression of HIV antigens and RNA during disease progression, and associations with histopathologic alterations, clinical symptoms, and immune alterations. The changes were greatest in HIV-infected individuals without AIDS. We hypothesize that intestinal mucosa is a preferred reservoir for HIV and a site where lymphocytes become infected and are destroyed. The process is chronic and self-perpetuating due to the proximity of bacterial and other foreign antigens and to the altered release of cytokines which modulate HIV replication. However, the pathogenic importance of this process is not well defined. The aims of this proposal are to determine the cellular reservoirs and content of HIV DNA and RNA in intestinal mucosa, to determine if mucosal HIV RNA expression is related to intestinal symptoms, histopathologic alterations, and accelerated disease progression. The localization of HIV to areas of cellular injury will be sought to provide direct evidence of its role in intestinal disease. Studies will involve HIV-infected volunteers with and without symptoms and controls who are followed quarterly and undergo three GI evaluations over two years. Cellular reservoirs and mucosal viral content in mucosa and blood will be determined by RNA in situ hybridization, DNA and RNA template-specific polymerase chain reaction, in situ PCR, electron and immunoelectron microscopy, and immunohistology. Cells undergoing lysis via apoptosis or apparent syncytia formation will be identified and the presence of HIV determined by immunohistochemistry and immunoelectron microscopy. The relative importance of selected cytokines and specific anti-HIV immune functions in modulating mucosal HIV RNA production will be compared and a predictive model for HIV RNA expression derived. Demonstration of the importance of intestinal mucosa in disease progression may lead to better understanding of the mechanisms underlying lymphoid depletion and could lead to new therapeutic strategies.