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: 6348838
• 负责人: NEREIDA A PARADA
• 金额: $ 11.07万
• 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/6348838
• 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是在Parada博士的共同赞助者Drs. Center和Cruikshank的实验室中鉴定、表征和克隆的。IL-16的功能之一是选择性激活 CD 4 + T细胞。其他主要功能包括所有人的趋化活性 CD 4+白细胞，CD 4 + T细胞的感受态生长因子， 混合淋巴细胞反应和TcR活化，以及HIV-1抑制 复制的IL-16的所有功能都需要Cdr，它利用Cdr作为 其膜识别单元。这表明CD 4除了作为 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。CD 4的其他功能，即 趋化因子和生长因子受体通过与其 天然淋巴因子配体IL-16。Parada博士对IL-16的研究表明， 通过CD 4的信号传导可以独立于TcR和CD 3发生， 导致细胞迁移和细胞周期进展为IL-2 R、IL-2 R、G1 能力点。他们实验室最近的研究表明， 用IL-16和IL-2的组合治疗（超过四周）导致 表达IL-2 R的CD 4细胞的显著协同增加。 本研究旨在探讨IL-16诱导的CD 4- 与IL-2 R相关的转录因子的依赖性活化和IL-2 R 表情将进行下文所述的实验以鉴定IL-16。 IL-2 R和基因表达中的应答元件。这将使博士。 Parada学习和应用分子生物学技术，同时允许她 将自己定位为IL-16专家，并开展独立项目， 科学目标的逻辑延伸。