Ontogeny & Maintenance of Virus Specific T Cells

人们普遍认识到有效的艾滋病毒疫苗的紧迫性和重要性，但还有许多其他病毒疫苗需要开发或改进，如疱疹病毒、呼吸道病毒、肠道病毒、出血热等，仅举几例。分子生物学和细胞免疫学的显著进步为疫苗开发的新时代奠定了基础。该计划项目的目标是：1)检测病毒特异性T淋巴细胞对持续病毒感染(爱泼斯坦-巴尔病毒)和非持续病毒感染而不重复抗原暴露(牛痘)的诱导、进化和稳定性；2)研究无关抗原对病毒特异性记忆T淋巴细胞群体进化的影响；3)检查1和2中概述的跨年龄段的目标；计划项目格式提供了对人类病毒特异性记忆T淋巴细胞反应的全面了解，而不是研究人员单独工作所能达到的。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，并测试成人和儿童这种反应的性质将不同的假设，成人经常出现严重症状，儿童通常没有症状。项目2将测试这样一个假设，即不同病毒之间的交叉反应在病毒感染期间是常见的，并且以前遇到的病毒特有的记忆T细胞可能会被异种病毒感染激活。项目3将使用痘苗病毒感染作为一种系统来检查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/财政监督，并提供临床样本。四聚体核心将为CD8 T淋巴细胞分析提供人类白细胞抗原I类/多肽四聚体。细胞科学核心将提供试剂、细胞分离、细胞系的建立和维护。该计划将加深对人类体内病毒特异性T细胞反应的了解，这将促进人类使用的新的和改进的疫苗的开发。

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.