CLONING, ANALYSIS NON HUMAN PRIMATE CYTOKINES, IMMUNE RECEPTORS

最近的治疗尝试包括各种细胞因子， 造血生长因子，或用于调节的特定配体 免疫反应和造血功能用于治疗各种疾病 临床条件或作为免疫方案的佐剂。一个 大量这样的应用被研究使用不同的 非人灵长类动物模型，尽管大多数人为因素出现 在非人类灵长类动物中具有生物活性，数据显示注射 人类重组细胞因子通常不允许重复或 由于快速发展的免疫反应而进行的长期治疗 这些“外来”分子，导致失活和 清除这些细胞因子。此外，猪瘟的免疫应答 灵长类细胞对某些人类细胞因子的刺激 发现明显低于等效细胞的响应 人类起源。人们对细胞因子特别感兴趣。 决定论在调节免疫应答类型中的作用 包括SIV在内的某些病原体。因此，编码不同种类的 非人灵长类细胞因子被克隆和测序。此外，我们 已经将这样的分析扩展到新世界的Aotus猴子和共同 绒猴，以及东半球的狒狒。在这方面， 人们一直致力于表达重组猕猴IL-2， IL-4、IL-6、IL-10、IL-12、IL-15、IL-16、IL-18、IL-4、IL-6、IL-10、IL-12、IL-15、IL-16、IL-18、IL-4、IL-6、IL-18、IL-4、IL-6、IL-10、IL-12、IL-15、IL-16、IL-18、IL-4、IL-6、IL-10、IL-12、IL-16、IL-18、IL-4、IL-6、IL-10、IL-12、IL-16、IL-18、IL-4、IL-6、IL-10、IL-12、IL-16、IL-18、IL-4、IL-6、IL-10、IL-12、IL-16、IL-18、IL-4、IL-6、 此外，天然和修饰的C-C趋化因子的产生如下 抑制慢病毒感染的因素可能是通过下调 病毒进入的共同受体。重组猕猴IL-2、IL-4和IL-12 目前在体内被用来加强SIV免疫 与欧洲的两个研究团队以及Vogel博士的 美国国立卫生研究院的研究小组。目前还在对IL-12进行评估 希勒博士对感染SIV的猕猴的治疗作用 耶克斯中心。这些研究具有快速翻译的潜力 转化为治疗人类疾病的应用。 资助NIH/NIAID$21,228 8/01/98-7/31/99 C00 IPR Karen肯尼亚/CASE 加州大学旧金山分校西部大学海军神经生物学系 贝塞斯达医学研究所。出版物无

Recent therapeutic attempts include a variety of cytokines, hematopoietic growth factors, or specific ligands for the modulation of immune responses and hematopoiesis for the treatment of various clinical conditions or as adjuvant to immunization protocols. A significant number of such applications are studied using various nonhuman primate models, yet while most human factors appear biologically active in nonhuman primates, data shows that injection of human recombinant cytokines most often does not allow repeated or long-term treatment due to rapid development of an immune response towards these "foreign" molecules, resulting in inactivation and clearance of these cytokines. Furthermore the immune response of primate cells to the stimulation by certain human cytokines has been found to be markedly lower than the response of equivalent cells from human origins. There is a particular interest in cytokines that play a deterministic role in modulating the type of immu ne r esponse to certain pathogens including SIV. Therefore, cDNA coding for various nonhuman primate cytokines were cloned and sequenced. In addition, we have extended such analyses to new world aotus monkeys and common marmoset monkeys, as well as to old world baboons. In this regard, efforts have been devoted at expressing recombinant macaque IL-2, IL-4, IL-6, IL-10, IL-12, IL-15, IL-16, IL-18 TNF-(, Flt-3L and IFN(. In addition Native and modified C-C Chemokines were generated as these factors may block lentivirus infection by downregulating the coreceptor for viral entry. Recombinant macaque IL-2, IL-4 and IL-12 are currently being utilized in vivo to potentiate SIV immunizations in collaboration with 2 research teams in Europe and with Dr. Vogel's research group at the NIH. IL-12 is also currently being assessed therapeutically in SIV infected macaques with Dr. Hillyer at the Yerkes Center. These studies bear the potential to rapidly translate into therapeutic applications for th e treatment of human diseases. FUNDING NIH / NIAID $21,228 8/01/98 - 7/31/99 C00 IPR Karen Kenya/Case Western University UC San Francisco, Dept of Neurobiology, Naval Medical Research Institute, Bethesda. PUBLICATIONS None