Kasai M, Kumano K, Kurasawa K, Nakao A, Saito Y, Iwamoto I
Department of Internal Medicine II, Chiba University School of Medicine, Chiba City, Japan.
Int Arch Allergy Immunol. 1998 Sep;117 Suppl 1:14-9. doi: 10.1159/000053564.
To determine whether the costimulatory signal via CD28/B7 interaction is required for causing allergic inflammation, we examined the effect of administration of CTLA4-Ig, a fusion protein of the extracellular domain of CTLA4 and human IgG1-constant region, at the time of sensitization, on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on IL-2, IFN-gamma, IL-4 and IL-5 production in the airways of the mice and on antigen-specific IgE synthesis in the mice. Administration of CTLA4-Ig at the time of sensitization suppressed antigen-induced eosinophil infiltration into the trachea and antigen-specific IgE production in mice. Furthermore, CTLA4-Ig administration at the time of sensitization suppressed not only IL-2 production but also IFN&hyphengamma and Th2 cytokine IL-4 and IL-5 production in the airways. Because allergic inflammation requires CD4+ T cells producing Th2-type cytokines IL-4 and IL-5, our results suggest that the costimulatory signal via CD28/B7 interaction is important for the generation and activation of Th2 cells and thereby for the development of allergic inflammation.
为了确定通过CD28/B7相互作用的共刺激信号是否是引发过敏性炎症所必需的，我们研究了在致敏时给予CTLA4-Ig（CTLA4细胞外结构域与人IgG1恒定区的融合蛋白）对致敏小鼠气管中抗原诱导的嗜酸性粒细胞浸润、小鼠气道中IL-2、IFN-γ、IL-4和IL-5产生以及小鼠体内抗原特异性IgE合成的影响。在致敏时给予CTLA4-Ig可抑制抗原诱导的嗜酸性粒细胞向小鼠气管的浸润以及小鼠体内抗原特异性IgE的产生。此外，在致敏时给予CTLA4-Ig不仅抑制了IL-2的产生，还抑制了气道中IFN-γ以及Th2细胞因子IL-4和IL-5的产生。由于过敏性炎症需要产生Th2型细胞因子IL-4和IL-5的CD4 + T细胞，我们的结果表明通过CD28/B7相互作用的共刺激信号对于Th2细胞的产生和激活以及过敏性炎症的发展很重要。
