Hayashi S, Johnston S A, Takashima A
Department of Dermatology, University of Texas Southwestern Medical Center, 75235-9069, Dallas, TX, USA.
Vaccine. 2000 Jul 15;18(27):3097-105. doi: 10.1016/s0264-410x(00)00140-7.
Dendritic cell (DC)-based vaccines have been used to generate Th1-mediated, protective immunity against cancers and infectious microorganisms. As an attempt to develop a new vaccine protocol for the induction of Th2-directed responses, we introduced an IL-4 plasmid vector into the XS106 DC line (derived from A/J mice). Although relatively small fractions of XS106 cells exhibited apparent intracellular deposition of IL-4, they secreted biologically relevant amounts of the cytokine. IL-4-transduced XS106 DC and control XS106 DC transfected with vector alone were pulsed with KLH and injected s.c. into A/J mice. The overall magnitude of KLH-specific cellular and humoral responses was comparable between the two animal groups. However, they differed in the isotype profile albeit only transiently, with the IL-4-transduced DC group showing higher IgE and lower IgG2a responses, and in the cytokine profile, with spleen cells isolated from the IL-4-transduced DC group producing higher IL-13 and lower IL-12. Thus, delivery of IL-4 gene to relatively small numbers of DC is sufficient to modify the immunological outcome of DC-based vaccines.
基于树突状细胞(DC)的疫苗已被用于产生Th1介导的针对癌症和传染性微生物的保护性免疫。作为开发一种诱导Th2定向反应的新疫苗方案的尝试,我们将白细胞介素-4(IL-4)质粒载体导入XS106 DC细胞系(源自A/J小鼠)。尽管相对较小比例的XS106细胞表现出明显的IL-4细胞内沉积,但它们分泌了生物学上相关量的细胞因子。用钥孔戚血蓝蛋白(KLH)刺激经IL-4转导的XS106 DC和仅用载体转染的对照XS106 DC,然后皮下注射到A/J小鼠体内。在两个动物组之间,KLH特异性细胞和体液反应的总体强度相当。然而,它们在同种型谱方面有所不同,尽管只是短暂的,经IL-4转导的DC组显示出更高的IgE反应和更低的IgG2a反应,并且在细胞因子谱方面,从经IL-4转导的DC组分离的脾细胞产生更高的IL-13和更低的IL-12。因此,将IL-4基因传递给相对少量的DC足以改变基于DC的疫苗的免疫结果。