CD4 T cell respnse to Human herpesvirus-6

该项目是对CD4 T细胞对人类疱疹病毒6型（HHV-6）的反应的全面研究， 新出现/再出现的人类病原体。在大多数人中，儿童期的感染会平静地消退， 通过细胞免疫反应控制慢性终身感染。然而，病毒在 免疫抑制可导致严重疾病、神经系统并发症，甚至死亡， 器官移植后重要并发症该项目的一个目的是描述记忆T 细胞对这种慢性感染的反应，并将其与急性感染的反应进行比较。cd4和cd8t 对HHV-6的细胞应答将在健康的免疫供体和肾移植中表征 接受者经历病毒再激活。IL-10在调节这些反应中的可能作用是 研究了这些分析将涉及外周血和原代细胞系的离体分析，使用 功能测定和新开发的II类MHC寡聚体，并将与 项目2，研究小鼠中类似的CD4 T细胞功能亚群。第二个目标 该项目的目的是了解NK细胞在调节T细胞对HHV-6反应中的作用。初步数据 表明外周血中存在的NK群体调节对HHV-6应答的CD4 T细胞。几 将使用人外周血和原代细胞的离体分析来探索机制假说。 线这项工作将与项目1合作进行，该项目正在调查类似的纳戈尔诺-卡拉巴赫问题。 其他系统中的现象。该项目的第三个目的是研究和功能特性的CD4 T细胞对HHV-6的反应与其他病毒交叉反应。最近发现的几种HHV-6 T 细胞表位与其他常见病毒感染的表位相似。根据1998年 根据先前关于CDS交叉反应模式的工作，我们预测HHV-6特异性CD4 T细胞应答可以 识别由包括EBV、CMV和IAV的其它病毒引起的异源感染。这一预测将是 使用人外周血和原代细胞系的离体分析以及生物化学和 MHC和TCR蛋白的结构分析。将与项目3合作实现这一目标。

This project is a comprehensive look into the CD4 T cell response to human herpesvirus 6 (HHV-6), an emergent / re-emergent human pathogen. In most people infection in childhood resolves uneventfully to a chronic life-long infection held in check by cellular immune responses. However, viral reactivation after immunosuppression can cause serious illness, neurological complications, and even death, and is an important complication following organ transplantation. One aim of the project is to characterize memory T cell responses to this chronic infection, and compare them to responses to acute infection. CD4 and CDS T cell responses to HHV-6 will be characterized in healthy immune donors and also in kidney transplant recipients experiencing viral reactivation. A possible role for IL-10 in regulating these responses will be investigated. These analysis will involve ex vivo analysis of, peripheral blood and primary cell lines, using functional assays and newly-developed class II MHC oligomers, and will be pursued in collaboration with project 2, which is investigating analogous CD4 T cell functional subsets in mice. A second aim of the project is to understand the role of NK cells in regulating T cell responses to HHV-6. Preliminary data indicate that NK populations present in peripheral blood regulate CD4 T cells responding to HHV-6. Several mechanistic hypotheses will be explored using ex vivo analysis of human peripheral blood and primary cell lines. This work will be pursued in collaboration with project 1, which is investigating similar NK phenomenon in other systems. A third aim of the project is to investigate and functionally characterize CD4 T cell responses to HHV-6 that are cross-reactive with other viruses. Several recently identified HHV-6 T cell epitopes are similar to those from other common viral infections. Based on principles established in previous work on CDS cross-reactivity patterns, we predict that the HHV-6 specific CD4 T cell response can recognize heterologous infection by other viruses including EBV, CMV, and lAV. This prediction will be tested using ex vivo analysis of human peripheral blood and primary cell lines, and biochemical and structural analysis of MHC and TCR proteins. This aim will be pursued in collaboration with project 3.