Regulation of T Cells by the Cytokines IL-7 and IL-15

细胞因子 IL-7 和 IL-15 对 T 细胞的调节

• 批准号: 6693088
• 负责人: KIMBERLY D KLONOWSKI
• 金额: $ 4.73万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693088
• 关键词: Regulation; Cells; Cytokines; IL; 15

DESCRIPTION (provided by the applicant): Memory T cells are long-lived T cells which have previously encountered antigen and are poised for rapid response upon a secondary challenge. To date, the factor(s) involved in generating and maintaining the CD8 memory T cell pool remains an enigma. IL-7 is a well documented cytokine important for survival of CD8+T cells. Further, IL-15, a related cytokine, is also believed to be partially responsible for memory T cell development. The objective of this proposal is to evaluate the roles the two cytokines on memory T cell development and survival. To test whether IL-7 receptor (IL-7R) expression correlates with the generation of memory T cells, TCR transgenic IL-7R-alpha[hi] and IL-7R-alpha[lo] expressing activated T cells will be transferred into normal mice. Donor cell attrition and IL-7R expression will be monitored over time. Blocking experiments using an anti-IL7R-alpha mAb will pinpoint the stage at which IL-7 is essential for memory T cell generation. To look at the effects of both IL-7 and IL-15 on memory T cell development, memory T cells will be transferred into IL-15-/- mice followed by anti-IL-7R-alpha treatment. Together, these experiments will address the basic requirements for memory T cell development and may result in numerous clinical applications including augmenting vaccine efficacy.

描述（由申请人提供）：记忆T细胞是长寿命的T细胞，以前遇到过抗原，并准备好在二次挑战时快速反应。迄今为止，参与产生和维持CD8记忆T细胞池的因素仍然是一个谜。IL-7是一种对CD8+T细胞存活很重要的细胞因子。此外，IL-15，一种相关的细胞因子，也被认为部分负责记忆T细胞的发育。本研究的目的是评估这两种细胞因子在记忆T细胞发育和存活中的作用。为了检验IL-7受体（IL-7R）的表达是否与记忆性T细胞的产生相关，我们将TCR转基因表达活化T细胞的IL-7R- α [hi]和IL-7R- α [lo]转移到正常小鼠体内。供体细胞损耗和IL-7R表达将随时间监测。使用抗il - 7r - α单抗的阻断实验将精确定位IL-7对记忆T细胞生成至关重要的阶段。为了观察IL-7和IL-15对记忆T细胞发育的影响，将记忆T细胞转移到IL-15-/-小鼠体内，然后进行抗il - 7r - α治疗。总之，这些实验将解决记忆T细胞发育的基本要求，并可能导致许多临床应用，包括增强疫苗效力。