BASIC AIDS RELATED IMMUNOLOGY RESEARCH

艾滋病相关基础免疫学研究

• 批准号: 6116323
• 负责人: Edward A Clark
• 金额: $ 8.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116323
• 关键词: AIDS; Mammalia; Primates; animal tissue; genetics; immunology; infection; inflammation; lymphatic system; virus

The goal of this project is to study the regulation of dendritic cells (DCs) and immunodeficiency viruses. The year 1997 was very productive in our lab and resulted in a number of publications. We found that human immunodeficiency virus type I (HIV-1), like simian immunodeficiency virus, requires signaling of CD28 or IL-2 receptors in order to replicate in resting T cells and move to the nucleus to form LTR circles, i.e., set up a latent infection. This finding suggests that selective blockade of certain T cell signaling pathways may reduce virus load in HIV-infected individuals. We developed a method and model for isolating and characterizing macaque DCs and found that we can infect macaque DCs in vitro with HIV-2. We have isolated human blood DCs and found that CD4 ligation signals survival in DCs and makes them more effective antigen-presenting cells. We have also defined a set of genes that are induced after CD40 ligation of immature DCs, including the death receptor, TRAIL, and death caspase, caspase-7. A major effort will continue to be the definition of DC signaling pathways and discovery of how they are affected by HIVs. We reported a role for c-myc in B cell receptor induced death. A novel receptor that we helped to discover was given a new CD number, CDw150. Significant effort was spent on the preparation of review articles on DCs and their role in HIV pathogenesis and a chapter on the mechanisms of cellular cooperation to be published in an encyclopedia of immunology.

该项目的目的是研究树突状细胞（DC）和免疫缺陷病毒的调节。 1997年在我们的实验室中非常有生产力，并产生了许多出版物。 我们发现，人类免疫缺陷病毒I型（HIV-1），例如Simian免疫缺陷病毒，需要对CD28或IL-2受体的信号传导，以便在静止的T细胞中复制并移至细胞核以形成LTR圆圈，即建立潜在的感染。 这一发现表明，某些T细胞信号通路的选择性阻断可能会减少感染HIV感染的个体的病毒负荷。 我们开发了一种分离和表征猕猴DC的方法和模型，发现我们可以在体外用HIV-2感染猕猴DC。 我们已经分离了人类血液DC，发现CD4连接信号在DC中存活，并使它们更有效地呈现抗原的细胞。 我们还定义了一组基因，这些基因是在未成熟DC的CD40连接后诱导的，包括死亡受体，小径和死亡caspase，caspase-7。 主要的努力将继续是DC信号通路的定义，并发现它们如何受到艾滋病毒的影响。 我们报道了C-MYC在B细胞受体诱导死亡中的作用。 我们帮助发现的一种新颖的受体得到了新的CD编号CDW150。 在准备有关DC的审查文章及其在HIV发病机理中的作用以及有关细胞合作的机制的综述文章花费了重大努力，该章节将在免疫学百科全书中发表。