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内源性IL-12决定人PBMC产生干扰素γ的水平(英)

Endogenous production of IL-12 is critical for optimal production of interferon-γ by human PBMC

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【作者】 孙晗笑杨滨燕李波娄阁吴长有

【Author】 SUN Han-Xiao , YANG Bin- Yan , LI Bo , LOU Ce, WU Chang- You. Center for Genomic Medicine Research, Medical College, Jinan University, Guangzhou 510632

【机构】 暨南大学医学院基因组药物研究中心University of MarylandHarbin Medical UniversityCellular Immunology SectionVaccine Research CenterNational Institutes of Health 广州510632广州510632College parkUSAHarbin 150

【摘要】 目的:IFN-γ是由被有丝分裂原或抗原所激活的T细胞和NK细胞所产生,它具有广泛的免疫调节活性,现认为IL-12(外源性)是诱导 IFN-γ产生的强诱导剂,并可促进静息 CD4+T细胞朝向 Th1表型分化,即诱导细胞免疫。目的是为了解由PBMC产生的内源性IL-12是否在体外可诱导IFN-γ的产生及通过何机制诱导细胞免疫。方法:用抗CD3抗体、PHA、抗CD3抗体加抗CD28抗体和抗原(MLC)来检测被刺激的PBM细胞的IFN-γ的产生,同时也用IL-12和IL-12Rβ1的中和抗体来抑制IFN-γ的产生。结果:激活的人PBM中IFN-γ分泌依赖于内源性IL-12的产生,而且激活的T细胞可诱导APC细胞产生IL-12,此过程是通过T细胞表面的CD40L和APC的CD40相互作用而实现。结论:这些结果提示,内源性IL-12在正常宿主抗细胞内抗原的感染反应中起重要作用,在某些形式的自身免疫性疾病和移植排斥反应的免疫病理发生中也起中心作用。

【Abstract】 Objective: IFN-y is produced by both activated T and NK cells in response to mitogen or antigen and has a broad range of immunoregulatory activity. IL-12 has been described as a strong inducer of IFN-γproduction and promotes the differentiation of naive CD4+T cells toward the Th1 phenotype, priming them for IFN-γproduction, and consequent induction of cell-mediated immunity. Aim is to know endogenous production of IL,12 from PBMC inducing production of IFN-γin vitro, which is involving in mechanism of T cells to be activated. Methods: Induced IFT-γ secretion from human PBMC by stimulated with anti-CD3 , PHA, anti-CD3 plus anti-CD28 and antigen(MLC) Also inhibited IFN-γproduction by neutralizing antibodies to IL-12 and IL-12Rβ1 significantly. Results: IFN-γsecretion from human activated PBMC is endogenous IL-12dependent, and activated T cells induce the production of IL-12 from APC by a mechanism involving the interaction between CD40L on T cells and CD40 on APC. Conclusion: These results suggest that endogenous IL-12 plays an important role in the normal host defense against infection by a variety of intracellular pathogens and also plays a central role in the genesis of some forms of immunopathology including autoimmune diseases and transplantation rejections.

【关键词】 白细胞介素12IFN-γCD40L
【Key words】 IL-12 IFN-γCD40L
【基金】 National Nature Science Foundation of China (30170881 and 30070697) ;Nature Science Foundation of Guangdong Province(990470)
  • 【文献出处】 中国免疫学杂志 ,Chinese Journal of Immunology , 编辑部邮箱 ,2002年04期
  • 【分类号】R392.11
  • 【被引频次】5
  • 【下载频次】127
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