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.

生物体对感染因子的反应涉及复杂的过程 不同细胞类型之间的相互作用，这些细胞类型通常受到各自的调节 通过可溶性因子或细胞因子网络发挥作用。 细胞因子反应 有助于调节炎症、迁移和功能 激活自然抵抗效应细胞，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 刺激因子或白细胞介素 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 细胞通过诱导淋巴因子的产生，特别是 干扰素-y (IFN-y)、增殖以及特异性和非特异性的增强 特异性细胞毒活性。 初步证据表明， NKSF/IL-12 在内毒素休克和辅助性 T (TH) 1 调节中的作用 Th2 免疫反应。 在这些研究的基础上，建议 NKSF/IL-12 通过在吞噬细胞和吞噬细胞之间提供信号传导桥梁 淋巴细胞在炎症和免疫调节中发挥着关键作用 回复。 为了分析这个假设，机制 将通过表征来分析 NKSF/IL-12 生产的调节 人体外周血和其他器官中的细胞以及人体细胞 能够表达 NKSF/IL-12 两条链 mRNA 并产生 NKSF/IL-12 蛋白响应各种刺激和抑制 刺激并通过研究转录或转录后 参与调节 NKSF/IL-12 产生的分子机制。 NKSF/IL-12对T淋巴细胞和NK细胞的生物学作用 还可以通过研究 a) NKSF/IL-12 的能力来进行调查 异二聚体与表面受体相互作用，介导信号 转导和调节编码蛋白质的基因表达很重要 淋巴细胞分化、增殖和功能； b) 的 NKSF/IL-12 调节 IFN-γ 基因的机制； c) 角色 NKSF/IL-12 在调节人 TH1 和 TH2 细胞分化中的作用。