Control of high avidity CTL differentiation

高亲和力 CTL 分化的控制

• 批准号: 6921504
• 负责人: ELLEN M PALMER
• 金额: $ 5.35万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-16 至 2006-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6921504
• 关键词: CD40 molecule; Paramyxovirus; antigen presenting cell; cell differentiation; cytokine; cytokine receptors; cytotoxic T lymphocyte; enzyme linked immunosorbent assay; helper T lymphocyte; intermolecular interaction; laboratory mouse; leukocyte activation /transformation; postdoctoral investigator; receptor expression; simian virus; tissue /cell culture; western blottings

DESCRIPTION (provided by the applicant): The functional avidity of a CD8+ T cell correlates with the magnitude of its effector function. High avidity are more effective than low avidity CD8+ T cells in clearing virus in vivo. Antigen density is one factor that controls avidity, however it is likely that other factors are involved in the determination of avidity. The goal of these studies is to determine the role of CD4+ T helper cells in the generation of a high avidity CD8+ T cells following intranasal immunization of mice with the paramyxovirus simian virus 5. In this model, the number of high avidity CD8+ T cells is severely reduced in CD4-depleted mice, suggesting that CD4+ T cell "help" provided by CD40/CD40L-mediated APC activation and/or cytokine secretion influence CD8+ T cell avidity. The role of APC activation in the generation of CD8+ T cell avidity will be determined in mice deficient for CD40. The role of T helper cytokines in the generation of high avidity CD8+ T cells will be determined by identifying candidate cytokines and analyzing cytokine receptor expression on CD8+ T cells. The necessity and sufficiency of the candidate cytokine for high avidity CD8+ T cell responses will also be assessed. These studies will determine whether APC-derived signals and/or cytokines promote the activation, survival or expansion of high avidity CD8+ T cells. Knowledge of the factors that control the functional avidity may lead to more efficacious vaccines that elicit high avidity CD8+ T cell responses.

描述（由申请人提供）：CD8+ T细胞的功能亲和力与其效应函数的大小相关。高潮比在体内清除病毒中比低流动性CD8+ T细胞更有效。抗原密度是控制亲和力的一个因素，但是可能参与了同性恋的确定。这些研究的目的是确定CD4+ T辅助细胞在使用帕托马伏病毒邻苯二醇病毒5的小鼠免疫后产生高流行病CD8+ T细胞中的作用。在该模型中，高流行病CD8+ T细胞的数量严重降低了CD4+ T细胞中的CD4+ T细胞中的CD4+ TIRVID/CD4/cd40 0，或者由CD4/cd4 hers cd 40/0。细胞因子分泌会影响CD8+ T细胞的亲和力。 APC激活在CD8+ T细胞生成中的作用将在缺乏CD40的小鼠中确定。 T辅助细胞因子在高自发CD8+ T细胞产生中的作用将通过鉴定候选细胞因子并分析CD8+ T细胞上的细胞因子受体表达来确定。还将评估候选候选细胞因子的必要性和足够性CD8+ T细胞反应。这些研究将确定APC衍生的信号和/或细胞因子是否促进了高潮CD8+ T细胞的激活，存活或扩展。了解控制功能亲和力的因素可能会导致更有效的疫苗引起高潮CD8+ T细胞反应。