REGULATION OF IL-2 RECEPTOR BY THE CD4 LIGAND IL-16

CD4 配体 IL-16 对 IL-2 受体的调节

• 批准号: 6532868
• 负责人: NEREIDA A PARADA
• 金额: $ 11.88万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6532868
• 关键词: cytokine receptors; gene expression; helper T lymphocyte; interleukin 2; lymphokines; receptor expression; transcription factor

IL-16 was identified, characterized and cloned in the laboratory of Dr. Parada's co-sponsors, Drs. Center and Cruikshank. One of the functions of IL-16 is a selective activation for CD4+ T cells. Other major functions include chemotactic activity for all CD4+ leukocytes, a competence growth factor for CD4+ T cells, inhibition of the mixed lymphocyte reaction and TcR activation, and inhibition of HIV-1 replication. All of IL-16`s functions require Cdr which it utilizes as part of its membrane recognition unit. Suggesting that CD4 has functions other than as the recognized intercellular adhesion molecule complementary to MHC II molecules during antigen presentation. These other functions of CD4, namely as a chemotactic and growth factor receptor are mediated by interaction with its natural lymphokine ligand, IL-16. Dr. Parada's studies with IL-16 demonstrate that signaling through CD4 can take place independent of the TcR and CD3 and result in cell migration and cell cycle progression to an IL-2R, IL-2R, G1 competence point. Recent studies in their laboratory have shown that long term treatment (over four weeks) with a combination of IL-16 and IL-2 leads to a dramatic synergistic increase in CD4 cells expressing IL-2R. This proposal will explore the relationship between IL-16 induced CD4- dependent activation of transcription factors associated with IL-2R and IL-2R expression. Experiments described below will be performed to identify IL-16- responsive elements within the IL-2R and gene expression. This will allow Dr. Parada to learn and apply molecular biology techniques while allowing her to establish herself as an IL-16 expert with an independent project that is a logical extension of her scientific goals.

IL-16 在 Parada 博士的共同发起人 Drs. 的实验室中进行了鉴定、表征和克隆。中心和克鲁克香克。 IL-16的功能之一是选择性激活 对于 CD4+ T 细胞。其他主要功能包括所有趋化活性 CD4+白细胞，CD4+T细胞的活性生长因子，抑制 混合淋巴细胞反应和 TcR 激活以及 HIV-1 的抑制 复制。 IL-16 的所有功能都需要 Cdr，它用作 它的膜识别单元。表明 CD4 具有除 as 以外的功能 公认的与 MHC II 互补的细胞间粘附分子 抗原呈递过程中的分子。 CD4 的这些其他功能，即 趋化因子和生长因子受体是通过与其相互作用介导的 天然淋巴因子配体，IL-16。 Parada 博士对 IL-16 的研究表明 通过 CD4 发出的信号可以独立于 TcR 和 CD3 发生，并且 导致细胞迁移和细胞周期进展为 IL-2R、IL-2R、G1 能力点。他们实验室最近的研究表明，长期来看 IL-16 和 IL-2 联合治疗（超过 4 周）可导致 表达 IL-2R 的 CD4 细胞显着协同增加。 该提案将探讨 IL-16 诱导的 CD4- 之间的关系 与 IL-2R 和 IL-2R 相关的转录因子的依赖性激活 表达。将进行下述实验来鉴定IL-16- IL-2R 和基因表达中的反应元件。这将使博士。 帕拉达学习并应用分子生物学技术，同时让她能够 通过一个独立项目确立了自己作为 IL-16 专家的地位 她的科学目标的逻辑延伸。