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 细胞记忆的产生是保护性免疫的关键组成部分。虽然记忆 T 细胞通常是在用外来抗原启动幼稚 T 细胞后产生的，但独特的途径也可以产生功能性记忆 T 细胞 - 作为淋巴细胞减少环境中稳态增殖的结果。对稳态增殖产生的记忆 T 细胞（“HP 记忆”细胞）的研究有助于了解记忆 T 细胞分化的基本要求，也有助于评估这种替代途径在免疫受损个体中建立保护性免疫的相关性。我们最近使用小鼠模型表明，“传统记忆”T 细胞（即通过启动产生的细胞）和 HP 记忆 CD8 T 细胞都提供类似的针对病原体的保护性免疫。然而，虽然淋巴细胞减少症的实验模型得到了充分研究，但对淋巴细胞减少症自然情况下（新生儿期和急性感染后）产生的 HP 记忆细胞知之甚少。我们通过三个目标对此进行探索，研究：在“自然”淋巴细胞减少环境中生成的 HP 记忆 CD8 T 细胞的功能（目标 1）：抗原特异性内源性 HP 记忆 CD8 T 细胞的存在和功能（目标 2）以及新生儿淋巴细胞减少和内源性 HP CD8 记忆 T 细胞在支持幼年动物免疫反应中的作用（目标 3）。这些研究的目的是确定外源抗原反应性 HP 记忆 CD8 T 细胞是否在淋巴细胞减少症自然发作期间产生，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 细胞是针对病原体的免疫保护的关键要素。记忆细胞是由于免疫启动而产生的，但也在对免疫缺陷或淋巴细胞减少的反应过程中产生，免疫缺陷或淋巴细胞减少是在发育过程中生理上发生的，也是感染的结果。该提案的意义在于了解这种“稳态”机制如何促进免疫功能低下个体（包括幼儿）建立保护性“记忆样”CD8 T 细胞系统。