Ontogeny & Maintenance of Virus Specific T Cells

研制有效的艾滋病毒疫苗的紧迫性和重要性得到了广泛认可，但许多其他病毒疫苗还需要开发或改进;疱疹病毒;呼吸道病毒;肠道病毒;出血热;仅举几例。分子生物学和细胞免疫学的显著进展为疫苗开发的新时代奠定了基础。本研究的主要目的是：1）研究病毒特异性T淋巴细胞对持续性病毒感染的反应的诱导、进化和稳定性（EB病毒）和非持续性病毒感染，而没有重复抗原暴露（牛痘）研究无关抗原对病毒特异性记忆T淋巴细胞群进化的影响; 3）检查1和2中概述的目标在整个年龄范围内;该计划项目格式提供了一个全面了解病毒特异性记忆T淋巴细胞反应的承诺，而不是孤立地工作的研究人员所能实现的。项目#1将扩展我们对EBV表位特异性CTL反应的定量和定性分析，并测试这种反应的性质在成人（通常出现严重症状）和儿童（通常无症状）中不同的假设。项目#2将测试这样的假设：不同病毒之间的交叉反应性T细胞反应在病毒感染期间很常见，并且针对先前遇到的病毒的特异性记忆T细胞可能会被异源病毒感染激活。项目#3将使用牛痘病毒感染作为一个系统来检查T细胞对一生中只遇到一次的非持久性病毒的反应。三个核心设施将促进这些项目的工作。行政和临床核心将提供科学/财务监督并提供临床样本。Tetramer Core将为CD 8 T淋巴细胞检测提供HLA I类/肽四聚体。细胞科学核心将提供试剂，细胞分离，细胞系的建立和维护。该计划将导致对人类病毒特异性T细胞反应的更深入了解，这将有助于开发用于人类的新的和改进的疫苗。

The urgency and importance of an effective vaccine for HIV is widely appreciated yet many additional viral vaccines are in need of development or improvement; herpesviruses; respiratory; enteric viruses; Hemorrhagic fevers; to name only a few. Remarkable advances in molecular biology and cellular immunology have set the stage for a new era of vaccine development. The goals of this program project are these: 1) To examine the induction, evolution, and stability of virus-specific T lymphocyte responses to a persistent virus infection (Epstein-Barr Virus) and to a non-persistent virus infection without repeated antigenic exposure (vaccinia); 2) To study the effects of unrelated antigens on the evolution of virus-specific memory T lymphocyte populations; 3) To examine the goals outlined in 1 and 2 across the age spectrum; The Program Project format affords the promise of generating a comprehensive understanding of virus-specific memory T lymphocyte responses in humans than could be achieved by investigators working in isolation. Project #1 will extend our quantitative and qualitative analyses of the EBV epitope-specific CTL response and test the hypothesis that the nature of this response will be different in adults, who often develop severe symptoms, and children, who are often asymptomatic. Project #2 will test the hypothesis that crossreactive T cell responses between different viruses are common during viral infections and that memory T cells specific to previously encountered viruses may become activated by a heterologous virus infection. Project #3 will use vaccinia virus infection as a system to examine T cell responses to a non-persistent virus only encountered once in a lifetime. Three Core Facilities will facilitate the work of these projects. The Administrative and Clinical Core will provide scientific/fiscal oversight and provide clinical samples. The Tetramer Core will provide HLA Class I/peptide tetramers for CD8 T lymphocyte assays. The Cell Science Core will provide reagents, cell separation, establishment and maintenance of cell lines. This Program will result in a deeper understanding of virus-specific T cell responses in humans, which will facilitate the development of new and improved vaccines for use in humans.