IMMUNOBIOLOGY OF INTERLEUKIN 12

有机体对感染性病原体的反应涉及一个复合体。 不同细胞类型的相互作用，这通常是在他们的 通过一系列可溶的因子或细胞因子发挥作用。细胞因子反应 有助于调节炎症、迁移和功能 激活天然抵抗力的效应细胞以及 T、B淋巴细胞的分化、增殖和活化， 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)是一种新型的异二聚体 细胞因子，由吞噬细胞和B细胞产生，作用于T细胞 细胞和NK细胞通过诱导淋巴因子的产生，特别是 干扰素-γ与特异性和非特异性干扰素的增殖和增强 特定的细胞毒活性。初步证据表明， NKSF/IL-12在内毒素休克中的作用及对辅助性T细胞(TH)1的调节作用 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 淋巴细胞在炎症和免疫调节中起着关键作用 回应。为了分析这一假说， NKSF/IL-12生产的调节将通过表征 人类外周血和其他器官中的细胞以及人类细胞 能表达NKSF/IL-12两条链的细胞株 NKSF/IL-12蛋白对多种刺激和抑制的反应 并通过研究转录或转录后的 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 也通过研究a)NKSF/IL-12的能力进行调查 异源二聚体与表面受体相互作用，介导信号 转导和调节编码重要蛋白质的基因的表达 在淋巴细胞分化、增殖和功能方面；b) NKSF/IL-12调节干扰素-γ基因的机制；以及c)作用 NKSF/IL-12对人TH1、TH2细胞分化的调控作用

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.