INTERFERON ALPHA AND HIV PATHOGENESIS

获得性免疫缺陷综合征(AIDS)是由感染 人类免疫缺陷病毒(HIV-1)。艾滋病的特点是 感染者体内的深部和/或肿瘤。除了……之外 艾滋病患者T单核细胞产生干扰素的缺陷- 阿尔法对感染单纯疱疹病毒1型的成纤维细胞的反应 被观察到了。这一缺陷与存在密切相关。 在研究的患者中的OI，也可以预测后续的OI。 对于那些尚未达到艾滋病病例定义的人来说，这是一个上升期。这些细胞 负责产生干扰素的人被发现是低密度的人类白细胞抗原-DR 阳性细胞与外周血树突状细胞表型相同 细胞。在本申请中，将进行研究，以 阳性鉴定产生干扰素的细胞，确定 HIV与这一人群的相互作用并确定 艾滋病和OI患者的干扰素-α产生不足。因为 DR阳性细胞只占单个核细胞的一小部分， 密度梯度技术与单抗的序贯耗竭 抗体将被用于浓缩。干扰素产生频率 细胞将通过免疫空斑试验和干扰素基因的表达进行监测 激活的细胞将通过S1映射来测量。免疫细胞化学和 利用抗人干扰素抗体的电子显微镜免疫金标技术 允许直接检测产生干扰素-α的细胞的形态。 将使用浓缩的干扰素-α产生细胞来确定 艾滋病毒在这些人群中的传播。艾滋病毒是否会复制和/或杀死这些人 细胞将被确定，艾滋病毒对功能分析的影响将是 调查过了。最后，对补肾益气的机理进行了评价。 将在艾滋病患者中进行干扰素-α的产生。干扰素-α 从艾滋病患者身上生产细胞将使用技术进行评估 在此应用和涉及共培养的功能研究中开发 为了寻找可能的抑制细胞或因子，将进行。 总之，拟议的涉及基础生物学和患者的实验 研究应该提供关于重要信息的重要信息 艾滋病的发病机制。

The Acquired Immune Deficiency Syndrome (AIDS) results from infection with the human immunodeficiency virus (HIV-1). AIDS is characterized by profound and/or neoplasms in the infected individual. In addition to deficiencies in T mononuclear cells from AIDS patients to make interferon- alpha in response to herpes simplex virus type-1 infected fibroblasts has been observed. This deficiency was strongly correlated with the presence of OI in the patients studied and was also predictive of OI in the follow- up period for those not yet meeting the AIDS case definition. The cells responsible for IFN-alpha production were found to be light density HLA-DR positive cells and shared the phenotype of peripheral blood dendritic cells. In the present application, studies will be undertaken to positively identify the IFN-alpha producing cells, determine the interaction of HIV with this population and determine the mechanism of deficient IFN-alpha production in patients with AIDS and OI. Because the DR-positive cells represent only a small fraction of the mononuclear cells, density gradient techniques and sequential depletions with monoclonal antibodies will be utilized for enrichment. Frequency of IFN-producing cells will be monitored by immunoplaque assay and IFN-gene expression in activated cells will be measured by S1 mapping. Immunocytochemical and immuno-gold techniques for electron microscopy using antibodies to IFN will allow for direct detection of morphology of IFN-alpha producing cells. Enriched IFN-alpha producing cells will be used to determine the effect of HIV on these populations. Whether HIV replicates in and/or kills these cells will be determined and the effect of HIV on functional assays will be investigated. Finally, an evaluation of the mechanism of deficiency of IFN-alpha production in AIDS patients will be undertaken. IFN-alpha producing cells from AIDS patients will be evaluated using techniques developed in this application and functional studies involving co-culture to look for possible suppressor cells or factors will be performed. Together, the proposed experiments involving both basic biology and patient studies should provide important information regarding an important mechanism of AIDS pathogenesis.