IMMUNOBIOLOGY OF INTERLEUKIN 12

白细胞介素 12 的免疫生物学

• 批准号: 2653831
• 负责人: GIORGIO TRINCHIERI
• 金额: $ 31.21万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2653831
• 关键词: T lymphocyte; biological signal transduction; cell differentiation; gene expression; genetic transcription; helper T lymphocyte; human tissue; interferon gamma; interleukin 12; laboratory mouse; leukocyte activation /transformation; natural killer cells; protein biosynthesis; receptor binding; tissue /cell culture; transfection

The response of the organism to infectious agents involves a complex interaction of different cell types, which are often regulated in their function by a network of soluble factors or cytokines. Cytokine response is instrumental in regulating inflammation, migration and functional activation of effector cells of natural resistance, as well as differentiation, proliferation and activation of the T and B lymphocytes, the effector cells of cellular and humoral adaptive immunity. NK cell stimulatory factor or interleukin 12 (NKSF/IL-12) is a novel heterodimeric cytokine, that is produced by phagocytic cells and B cells and acts on T cells and NK cells by inducing production of lymphokines, particularly interferon-y (IFN-y), proliferation, and enhancement of specific and non- specific cytotoxic activity. Preliminary evidence suggests a role for NKSF/IL-12 in endotoxin shock and in regulation of T helper (TH) 1 versus Th2 immune responses. On the basis of these studies, it is proposed that NKSF/IL-12 by providing a signaling bridge between phagocytic cells and lymphocytes plays a key role in regulation of inflammation and immune response. In order to analyze this hypothesis, the mechanisms of regulation of NKSF/IL-12 production will be analyzed by characterizing the cells in human peripheral blood and other organs as well as the human cell lines able to express mRNA for the two chains of NKSF/IL-12 and to produce NKSF/IL-12 proteins in response to various stimulatory and inhibitory stimuli and by studying the transcriptional or posttranscriptional molecular mechanisms involved in the regulation of NKSF/IL-12 production. The biological effects of NKSF/IL-12 on T lymphocytes and NK cells will also be investigated by studying a) the ability of the NKSF/IL-12 heterodimer to interact with surface receptors, mediate signal transduction, and regulate expression of genes encoding proteins important in lymphocyte differentiation, proliferation, and functions; b) the mechanisms of regulation of the IFN-y gene by NKSF/IL-12; and c) the role of NKSF/IL-12 in regulating differentiation of human TH1 and TH2 cells.

生物体对传染剂的反应涉及复杂 不同细胞类型的相互作用，这些类型通常在其中受到调节 可溶性因子或细胞因子网络的功能。 细胞因子反应 有助于调节炎症，迁移和功能 自然电阻的效应细胞的激活以及 T和B淋巴细胞的分化，增殖和激活， 细胞和体液适应性免疫的效应细胞。 NK细胞 刺激因子或白介素12（NKSF/IL-12）是一种新型异二聚体 细胞因子，由吞噬细胞和B细胞产生，作用于T 细胞和NK细胞通过诱导淋巴细胞的产生，特别是 干扰素 - Y（IFN-Y），比较和非 - 的增殖和增强 特定的细胞毒性活性。 初步证据表明 内毒素休克中的NKSF/IL-12和T辅助器（Th）1与 TH2免疫反应。 根据这些研究，有人提出 NKSF/IL-12通过在吞噬细胞和 淋巴细胞在调节炎症和免疫中起关键作用 回复。 为了分析这一假设， NKSF/IL-12的调节将通过表征来分析 人外周血和其他器官以及人类细胞中的细胞 能够表示NKSF/IL-12的两个链的线条并产生 NKSF/IL-12蛋白响应各种刺激和抑制作用 刺激并通过研究转录或转录后 NKSF/IL-12产生的调节涉及的分子机制。 NKSF/IL-12对T淋巴细胞和NK细胞的生物学作用将 也可以通过研究a）NKSF/IL-12的能力来研究 异二聚体与表面受体相互作用，介导信号 转导并调节编码蛋白质重要的基因表达 在淋巴细胞分化，增殖和功能中； b） NKSF/IL-12对IFN-Y基因调节的机制； c）角色 NKSF/IL-12在调节人Th1和Th2细胞的分化方面。