HIV INDUCED SYNCYTIA AND THE ORAL MANIFESTATIONS OF AIDS

描述：这一提议是基于这样一种断言，即 T淋巴细胞和树突状细胞来源的合胞体在淋巴组织中的作用 在这些细胞类型的耗尽过程中起着至关重要的作用 艾滋病毒感染和艾滋病的后续表现。假说 合胞体在体内的运动行为可能与白色有关 血细胞死亡，在病毒的传播和退化中 HIV感染者CD4+T细胞下降时淋巴组织的变化 数字。在这项拟议的研究中，计划进行实验以测试 合胞体形成于腋窝淋巴结和腺样体或扁桃体组织 感染艾滋病毒的患者(T细胞数量下降)也表现出同样的情况 在体外形成的合胞体表现出病理行为。首先，一个 T细胞衍生的行为能力的详细表征 在体外形成的合胞体将完成。这将包括行为上的 描述T细胞来源的合胞体融合和 合胞体介导的T细胞趋化，肌动蛋白在T细胞趋化中的作用 这些行为和T细胞趋化剂的特征 由合胞体释放。第二，运动行为将被确定为 从粘膜上皮分离朗格汉斯细胞并形成合胞体 通过HIV感染朗格汉斯细胞和T细胞。这 特征将包括：计算机辅助的易位分析 以及F-肌动蛋白的动态形态、运动周期、组织和 微管、核形态和化学诱导剂的释放。第三, 合胞体将从腋窝淋巴结和腺样体分离出来或 HIV感染志愿者的扁桃体组织中T细胞数量下降。 我们将测试这些设备的行为特征，以确定 合胞体在体外。T细胞和朗格汉斯细胞的体内机制 枯竭是不被理解的。这是PI认为艾滋病毒引起的 合胞体的形成可能在这两种细胞的耗尽中起作用。 以及存在批判性分析行为的需要 这种合胞体的表型，以评估它们在 疾病的发展。此外，合胞体的形成可能作为一种 艾滋病毒进展的迹象。

DESCRIPTION: This proposal is based upon the assertion that the formation of T lymphocyte and dendritic cell derived syncytia in lymphoid tissue plays a crucial role in the depletion of the these respective cell types during HIV infection and in the subsequent manifestations of AIDS. The hypothesis is that the motile behavior of syncytia in vivo may be involved in white blood cell death, in the dissemination of the virus, and in the degeneration of lymphoid tissue in HIV-infected patients with falling CD4+ T cell numbers. In the proposed research, experiments are planned to test whether syncytia formed in the axillary lymph node and adenoid or tonsillar tissue of HIV-infected patients (with falling T cells counts) exhibit the same pathological behaviors demonstrated for syncytia formed in vitro. First, a detailed characterization of the behavioral capabilities of T cell derived syncytia formed in vitro will be completed. This will include a behavioral description of the steps in T cell-derived syncytium fusion and syncytium-mediated T cell chemotaxis, an analysis of the role of actin in these behaviors and, a characterization of the T cell chemoattractant released by syncytia. Second, the motile behavior will be determined for Langerhans' cells isolated from mucosal epithelium and syncytia generated through HIV infection of Langerhans' cells and T cells. This characterization will include; a computer-assisted analysis of translocation and dynamic morphology, motility cycle, organization of F-actin and microtubules, nuclear morphology, and chemoattractant release. Third, syncytia will be isolated from the axillary lymph node and adenoid or tonsillar tissue of HIV-infected volunteers with falling T cell counts. These will be tested for the behavioral characteristics demonstrated for syncytia in vitro. The mechanisms in vivo for T cell and Langerhans' cell depletion are not understood. It is the belief of the PI that HIV-induced syncytium formation may play a role in the depletion of both cell populations and that a need exists to critically analyze the behavioral phenotype of such syncytia in order to assess their potential role in disease progression. Furthermore, syncytium formation may serve as an indication of HIV progression.