NONHUMAN PRIMATE CYTOKINES, CHEMOKINES & SECONDARY SIGNAL MOLECULES

编码各种细胞因子的cDNA被克隆并测序， 非人类灵长类动物 除了先前表征的IL-1 I之外， IL-1J、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12 I、IL-12 J、IL-15、 我们有来自猕猴和白眉猴的IFNK、TNFI、TGFJ和B7-1 将这些分析扩展到细胞因子IL-7、IL-16和IL-18， 趋化因子MIP-1 I、MIP-1 J、RANTES和SDF-1以及受体 CCR-2B、CCR-5、fusin、B7.2、CTLA-4与造血生长 因子GM-CSF、SCF和Flt 3-配体来描述差异 解释非人灵长类动物的表位差异和生物活性 细胞因子/趋化因子。 人们对细胞因子特别感兴趣 在调节免疫系统中起决定性作用 对包括SIV在内的某些病原体的反应。 在这方面， 致力于表达重组猕猴IL-2，IL-4，IL-10， IL-12、IL-15、IL-16、IL-18和IFNK，因为这些因子可能非常开放， 在广泛的医学应用中的有效治疗途径 例如移植、肿瘤学、血液学和传染病。 在这些领域中与人类相关的许多研究利用非人类 灵长类动物模型。 然而，最近的数据显示， 重组细胞因子通常不允许重复或长期使用。 治疗由于快速发展的免疫反应，对这些 “外来”分子，导致这些分子的失活和清除。 细胞因子 此外，灵长类动物细胞的免疫反应， 已经发现某些人细胞因子的刺激显著地 低于人类来源的等效细胞的反应。 目前正在利用重组猕猴IL-2、IL-4和IL-12 在体内加强SIV免疫与2 研究团队在欧洲和沃格尔博士的研究小组在 国家卫生研究院 IL-12目前也在SIV中进行治疗评估 和希利尔医生在耶基斯中心一起感染猕猴 此外，委员会认为， 通过与霍夫曼博士（NMRI，美国海军）合作，我们能够 表明单次注射IL-12足以预防 食蟹猴疟原虫感染的发展， 恒河猴 这些研究有可能迅速 转化为治疗人类疾病的治疗应用， 疾病

cDNAs coding for various cytokines were cloned and sequenced from nonhuman primates. In addition to the previously characterized IL-1I, IL-1J, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12I, IL-12J, IL-15, IFNK, TNFI, TGFJ and B7-1 from macaques and mangabeys, we have extended these analyses to the cytokines IL-7, IL-16 and IL-18, the chemokines MIP-1I, MIP-1J, RANTES and SDF-1 as well as the receptors CCR-2B, CCR-5, fusin, B7.2, CTLA-4 and the hematopoietic growth factors GM-CSF, SCF and Flt3-ligand to delineate differences accounting for epitope differences and bioactivity of nonhuman primate cytokines/chemokines. There is a particular interest in cytokines that play a deterministic role in modulating the type of immune response to certain pathogens including SIV. In this regard, efforts have been devoted at expressing recombinant macaque IL-2, IL-4, IL-10, IL-12, IL-15, IL-16, IL-18 and IFNK as these factors may open very potent therapeutic pathways in wide ranging cli nical applications such as transplantation, oncology, hematology and infectious diseases. Numerous studies related to humans in these fields utilize nonhuman primate models. Yet recent 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. 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. Furthermore, in collaboration with Dr. Hoff man (NMRI, US Navy), we were able to show that a single injection of IL-12 was sufficient to prevent development of infection by the malarial agent Plasmodium cynomolgi in rhesus macaques. These studies bear the potential to rapidly translate into therapeutic applications for the treatment of human diseases.