Homeostatic Proliferation and Memory CD8 T Cells

稳态增殖和记忆 CD8 T 细胞

• 批准号: 8051809
• 负责人: STEPHEN C JAMESON
• 金额: $ 35.8万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051809
• 关键词: Acute; Adoptive Transfer; Antigens; Appearance; CD8B1 gene; Cells; Development; Environment; Experimental Models; Fostering; Generations; Goals; Health; Immune; Immune response; Immune system; Immunity; Indium; Individual; Infection; Learning; Life; Light; Listeria monocytogenes; Lymphopenia; Memory; Mus; Neonatal; Newborn Animals; Pathway interactions; Property; Radio; Role; Staging; Stimulus; System; T cell differentiation; T cell response; T memory cell; T-Lymphocyte; Techniques; Testing; Work; interest; juvenile animal; mouse model; neonate; novel; pathogen; research study; response; young adult

DESCRIPTION (provided by applicant): Generation of T cell memory is a critical component of protective immunity. While memory T cells normally arise following priming of naove T cells with foreign antigen, a distinct pathway can also generate functional memory T cells - as a consequence of homeostatic proliferation in a lymphopenic environment. Study of memory T cells produced by homeostatic proliferation ("HP memory" cells) is relevant to understanding the essential requirements for memory T cell differentiation, and also for assessing the relevance of this alternative pathway in establishing protective immunity in immunocompromized individuals. Using mouse models, we recently showed that both "conventional memory" T cells (i.e. those generated through priming) and HP memory CD8 T cells offer similar protective immunity against a pathogen. However, while experimental models of lymphopenia are well studied, much less is known about HP memory cells produced during natural situations of lymphopenia (in the neonatal period and after acute infections). We explore this in three aims, studying: the function of HP memory CD8 T cells generated in "natural" lymphopenic environments (Aim 1): the presence and function of antigen specific endogenous HP memory CD8 T cells (Aim 2) and the role of neonatal lymphopenia and endogenous HP CD8 memory T cells in supporting immune reactivity of the young animals (Aim 3). The goal of these studies is to determine whether foreign antigen responsive HP memory CD8 T cells are generated during natural bouts of lymphopenia, and whether they contribute to the adaptive immune response. PUBLIC HEALTH RELEVENCE: Memory T cells are a critical element in immune protection against pathogens. Memory cells are generated as a consequence of immune priming, but are also generated during the response to immuno-deficiency, or lymphopenia, which occurs physiologically during development and also as a consequence of infections. The significance of the proposal is in learning how such "homeostatic" mechanisms may foster establishment of protective "memory- like" CD8 T cells system in immunocompromized individuals, including the very young.

描述（由申请人提供）：T细胞存储器的产生是保护性免疫的关键组成部分。尽管记忆T细胞通常是在用异物抗原启动NaOVE T细胞后出现的，但由于淋巴细胞增生环境中稳态增殖而导致的独特途径也可以产生功能性记忆T细胞。对稳态增殖产生的记忆T细胞的研究（“ HP记忆”细胞）与了解记忆T细胞分化的基本要求有关，也与评估该替代途径在免疫功能低下个体中建立保护性免疫方面的相关性有关。使用小鼠模型，我们最近表明，“常规记忆” T细胞（即通过启动生成的记忆）和HP记忆CD8 T细胞都提供了针对病原体的类似保护性免疫。但是，尽管对淋巴细胞减少症的实验模型进行了充分的研究，但对在淋巴细胞减少症的自然情况下产生的HP记忆细胞的了解少得多（在新生儿时期和急性感染后）。我们在三个目标中探讨了这一点：研究：HP记忆CD8 T细胞在“天然”淋巴尼分环境中产生的功能（AIM 1）：抗原特异性内源性内源性HP Memory CD8 T细胞的存在和功能（AIM 2）以及新生儿淋巴细胞减少症和内源性HP CD8记忆T细胞在支持免疫反应性的Younge Repactivity（AIM）3的作用。这些研究的目的是确定外国抗原反应性HP记忆CD8 T细胞是否在淋巴细胞学症的自然爆发过程中产生，以及它们是否有助于适应性免疫反应。公共卫生相关性：记忆T细胞是免疫保护病原体的关键因素。记忆细胞是由于免疫启动而产生的，但在对免疫缺陷或淋巴细胞减少症的反应过程中也会产生，这在发育过程中在生理上发生，也是由于感染而发生的。该提案的意义在于学习这种“稳态”机制如何促进免疫功能低下个体（包括非常年轻的人）中的CD8 T细胞系统建立保护性”记忆。