T CELL MEMORY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。免疫系统的非凡之处在于，它能够对各种各样的抗原产生反应，并对过去遇到的抗原做出更有力的反应。这种夸大的回忆免疫反应或免疫记忆是免疫学的一个核心概念，它构成了针对传染病的疫苗接种的基础。免疫记忆是由记忆淋巴细胞介导的，这些淋巴细胞在感染或抗原侮辱消退后长期存在于宿主体内。为了研究免疫记忆，我们开发了一种新颖而强大的转基因小鼠模型系统。在这个系统中，T淋巴细胞的效应池和记忆池都被不可逆转的基因重组事件标记为人胎盘碱性磷酸酶(PLAP)。我们的长期目标是了解免疫记忆是如何产生、调节和维持的。这项应用的目标是进一步验证转基因小鼠模型系统，并提出CD8 T细胞记忆是如何产生的基本问题，这是追求这一目标的第一步。这一应用的中心假设是抗原特异性效应器和记忆性CD8 T细胞可以被明确识别。我们将使用这个模型系统来探索淋巴细胞性脉络膜脑膜炎(LCMV)病毒诱导的免疫反应和免疫记忆产生的分化途径。我们期望，由此产生的方法将识别与CD8 T细胞记忆产生有关的关键事件。这项研究将具有重要意义，因为从这些研究中学到的东西将有助于更广泛地理解如何合理设计提供长期保护性免疫的疫苗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immune system is remarkable in its ability to mount responses against a wide array of antigens and to respond with enhanced vigor to antigens encountered in the past. This exaggerated recall immune response or immune memory is a central concept in immunology and it forms the basis of vaccination against infectious diseases. Immune memory is mediated by memory lymphocytes that persist in the host long after resolution of the infection or antigenic insult. To study immune memory, we have developed a novel and powerful transgenic mouse model system. In this system, both effector and memory pools of T lymphocytes are indelibly tagged with the marker, human placental alkaline phosphatase (PLAP) by an irreversible genetic recombination event. Our long-range goal is to understand how immune memory is generated, regulated and maintained. The objective of this application, which is the first step in pursuit of this goal, is to further validate the transgenic mouse model system and to ask fundamental questions about how CD8 T cell memory is generated. The central hypothesis of this application is that antigen-specific effector and memory CD8 T cells can be unambiguously identified. We will use this model system to probe lymphocytic choriomeningitis (LCMV) virus-induced immune responses and the differentiation pathway of immune memory generation. It is our expectation that the resultant approaches will identify key events involved in the generation of CD8 T cell memory. The research will be of significance because what is learned from these studies will contribute to broader understanding of how vaccines that provide long-term protective immunity can be rationally designed.