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

IL-16是在帕拉达博士的共同赞助人中心博士和克鲁克申克博士的实验室里鉴定、鉴定和克隆的。IL-16的功能之一是选择性激活 对于CD4T细胞。其他主要功能包括对所有人的趋化活动 CD4T细胞的活性生长因子--CD4白细胞的抑制作用 混合淋巴细胞反应和TCR激活与HIV-1的抑制 复制。IL-16的所有功能都需要CDR，它将其用作 它的膜识别单元。提示CD4具有AS以外的其他功能 公认的与MHC II互补的细胞间黏附分子 抗原呈递过程中的分子。CD4的这些其他功能，即作为 趋化和生长因子受体是通过与其相互作用而介导的 天然淋巴因子配体，IL-16。帕拉达博士对IL-16的研究证明 通过CD4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，从长远来看 联合使用IL-16和IL-2治疗(超过四周)可导致 协同作用使表达IL-2R的CD4细胞显著增加。 本方案将探讨IL-16诱导的CD_4~+、CD_4~-和CD_4~+细胞之间的关系。 IL-2R和IL-2R相关转录因子的依赖激活 表情。将进行以下实验以确定IL-16- IL-2R内的反应元件和基因表达。这将使Dr。 Parada学习和应用分子生物学技术，同时允许她 在一个独立的项目中确立自己作为IL-16专家的地位 她科学目标的合乎逻辑的延伸。

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.