Yanagihara Y, Kiniwa M, Koshio T, Kajiwara K, Yasueda H, Ikizawa K
Clinical Research Center for Allergy, National Sagamihara Hospital, Japan.
Int Arch Allergy Immunol. 1994 Oct;105(2):162-70. doi: 10.1159/000236819.
To study the regulatory mechanism of allergen-dependent human IgE synthesis, Cry j I-specific and interleukin 4 (IL-4)-producing CD4+ T cell lines (SN-4 and SS-12) were established from 2 patients allergic to Japanese cedar pollen who highly expressed IL-4 mRNA in T cells in response to Cry j I stimulation. Upon stimulation of SN-4 and SS-12 cells with Cry j I, IL-4 production, which was observed at the protein and the mRNA levels, was induced in an HLA-DR-restricted manner, using autologous and allogeneic antigen-presenting cells. In addition to IL-4, not only considerable amounts of IL-5 and IL-6 but also very small amounts of IL-2 and interferon-gamma (IFN-gamma) were secreted by SN-4 and SS-12 cells, indicating that they fit into the Th2-like phenotype. The culture supernatant from Cry j I-activated SN-4 cells had the ability to induce IL-4-dependent IgE synthesis, CD23 expression and soluble CD23 release. Moreover, Cry j I-dependent IgE synthesis medated by SN-4 cells derived from 1 patient expressing HLA-DRw8, w9 could be specifically induced in both autologous and HLA-DRw9-matched allogeneic B cell cultures. This IgE induction was inhibited by neutralizing antibodies to IL-4, IL-5 and IL-6, but was not enhanced by anti-IFN-gamma antibody. On the other hand, neither IL-4 production nor IgE synthesis was induced when SN-4 cells were cocultured in the presence of Cry j I with HLA-DRw8-matched or histoincompatible allogeneic cells.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究变应原依赖性人IgE合成的调节机制,从2例对日本柳杉花粉过敏的患者中建立了Cry j I特异性且产生白细胞介素4(IL-4)的CD4 + T细胞系(SN-4和SS-12),这2例患者的T细胞在Cry j I刺激下高表达IL-4 mRNA。用Cry j I刺激SN-4和SS-12细胞时,在蛋白质和mRNA水平均观察到IL-4的产生,使用自体和同种异体抗原呈递细胞以HLA-DR限制性方式诱导。除IL-4外,SN-4和SS-12细胞不仅分泌大量的IL-5和IL-6,还分泌极少量的IL-2和干扰素-γ(IFN-γ),表明它们符合Th2样表型。Cry j I激活的SN-4细胞的培养上清液具有诱导IL-4依赖性IgE合成、CD23表达和可溶性CD23释放的能力。此外,来自1例表达HLA-DRw8、w9的患者的SN-4细胞介导的Cry j I依赖性IgE合成可在自体和HLA-DRw9匹配的同种异体B细胞培养物中特异性诱导。这种IgE诱导被抗IL-4、IL-5和IL-6的中和抗体抑制,但不被抗IFN-γ抗体增强。另一方面,当SN-4细胞在Cry j I存在下与HLA-DRw8匹配或组织不相容的同种异体细胞共培养时,既不诱导IL-4产生也不诱导IgE合成。(摘要截短至250字)