REGULATION OF GENE EXPRESSION IN HUMAN T CELL BY INTERLEUKIN 12, 1, 18 AND TNF

许多巨噬细胞衍生的细胞因子，包括IL-1和TNF-α， 已发现其调节人T细胞的功能活性。 与IL-1和TNF-α一样，IL-12增强某些T细胞效应子功能， 特别是抗肿瘤活性。 尽管众所周知IL-12 在活化的T细胞中增强IFN-γ的合成， 对其他T细胞衍生的细胞因子的产生的影响还没有很好的定义。 在 在这个项目中，我们正在评估IL-12对表达的影响， 多种细胞因子，包括IFN-γ、IL-2、TNF-α和IL-10。 通过定义 在人T细胞中，IL-12刺激究竟诱导了哪些细胞因子 细胞，我们将获得更好的了解生物活动 这种强有力的细胞因子。 这些信息可能有助于评估 在未来的临床试验中观察到的任何治疗活性。 可能 也为某些毒性的生理基础提供了线索 与高剂量IL-12治疗有关。 白细胞介素-12（IL-12）是相对新近发现的细胞因子， 在活化的T细胞和NK细胞中放大IFN-γ的产生。 在 目前，关于IL-12对肿瘤细胞的作用知之甚少。 其他T细胞衍生的细胞因子的表达。 目前，IL-12 作为一种潜在的治疗剂，用于治疗许多 疾病，包括癌症和艾滋病毒感染。 它也被测试为 某些微生物疫苗的佐剂。 表征 IL-12对人T细胞中细胞因子表达的作用可以提供 关于这种细胞因子的作用机制的重要信息 增强体内各种免疫效应子功能。 它也可能有助于 CBER工作人员对IL-12的未来临床试验进行更严格的评估。 此外，分析IL-12对细胞因子表达的影响， 体外可鉴定IL-12活性的替代标记物， 在监测重组IL-12在人受体中的效力方面。

A number of macrophage-derived cytokines, including IL-1 and TNF-alpha, have been found to regulate the functional activities of human T cells. Like IL-1 and TNF-a, IL-12 potentiates certain T cell effector functions, particularly anti-tumor activities. Although it is well known that IL-12 amplifies IFN-gamma synthesis in activated T cells, its potential effects on production of other T cell-derived cytokines are not well defined. In this project, we are evaluating the effects of IL-12 on expression of multiple cytokines, including IFN-g, IL-2, TNF-a and IL-10. By defining exactly which cytokines are induced by IL-12 stimulation in human T cells, we will gain a greater understanding of the biological activities of this potent cytokine. This information may be useful when evaluating any therapeutic activity observed in future clinical trials. It may also provide clues to the physiological basis for certain toxicities associated with high dose IL-12 therapy. Interleukin-12 (IL-12) is a relatively recently discovered cytokine that amplifies production of IFN-gamma in activated T cells and NK cells. At present, relatively little is known about the effects of IL-12 on expression of other T cell-derived cytokines. IL-12 is currently being tested as a potential therapeutic agent for the treatment of a number of diseases, including cancer and HIV infection. It is also being tested as an adjuvant with certain microbial vaccines. Characterization of the effects of IL-12 on cytokine expression in human T cells may provide important information regarding the mechanism(s) by which this cytokine potentiates various immune effector functions in vivo. It may also help CBER staff to more critically evaluate future clinical trials of IL-12. Furthermore, analysis of the effects of IL-12 on cytokine expression in vitro may identify surrogate markers of IL-12 activity that may be useful in monitoring the potency of recombinant IL-12 in human recipients.