Victoratos P, Yiangou M, Avramidis N, Hadjipetrou L
Department of Genetics, Development and Molecular Biology, School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Greece.
Clin Exp Immunol. 1997 Sep;109(3):569-78. doi: 10.1046/j.1365-2249.1997.4631361.x.
Antibody isotype affects biological activity of the antibodies and therefore should be considered in prevention of disease by vaccination. In previous reports, we demonstrated that adjuvants affect the antibody isotype switching process and favour the production of certain isotypes. The present study extends these findings and shows fundamental differences in the cytokine induction pattern according to the adjuvant used. Cytokine mRNA levels were determined by in situ RNA-RNA hybridization performed on splenocytes isolated from mice injected with different adjuvants. The results revealed that Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), Al(OH)3 and QuilA administration results in a type-2 (humoral) response, increasing IL-4, IL-5 and IL-13 gene expression, while poly I:C exhibits a type-1 (cell-mediated) response, increasing the production of interferon-gamma (IFN-gamma), IL-2 and IL-6 mRNA. Finally, BeSO4 and poly A:U augment IL-5 and IL-6 mRNA production, while lipopolysaccharide (LPS) and LiCl augment IL-6 and tumour necrosis factor-alpha (TNF-alpha) mRNA production. Also, the adjuvants appear capable of overcoming the inherent IL-2/IFN-gamma and IL-4 dichotomy of C57B1/6 and BALB/c mice, respectively, in response to cellular antigens such as Leishmania and herpes simplex virus (HSV). The overall data suggest that adjuvants direct the isotype switching process via induction of certain cytokines, a finding that can be useful in selection of the most efficient isotype of protective antibodies for disease prevention by vaccination.
抗体亚型会影响抗体的生物学活性，因此在通过疫苗接种预防疾病时应予以考虑。在先前的报告中，我们证明佐剂会影响抗体亚型转换过程，并有利于某些亚型的产生。本研究扩展了这些发现，并显示了根据所用佐剂不同，细胞因子诱导模式存在根本差异。通过对从注射不同佐剂的小鼠分离的脾细胞进行原位RNA-RNA杂交来测定细胞因子mRNA水平。结果显示，弗氏完全佐剂（FCA）、弗氏不完全佐剂（FIA）、氢氧化铝（Al(OH)3）和QuilA的给药会导致2型（体液）反应，增加白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和白细胞介素-13（IL-13）基因表达，而聚肌胞苷酸（poly I:C）则表现出1型（细胞介导）反应，增加干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）和白细胞介素-6（IL-6）mRNA的产生。最后，硫酸铍（BeSO4）和聚腺苷酸:尿苷酸（poly A:U）增加IL-5和IL-6 mRNA的产生，而脂多糖（LPS）和氯化锂（LiCl）增加IL-6和肿瘤坏死因子-α（TNF-α）mRNA的产生。此外，佐剂似乎能够分别克服C57B1/6和BALB/c小鼠对细胞抗原（如利什曼原虫和单纯疱疹病毒（HSV））固有的IL-2/IFN-γ和IL-4二分法。总体数据表明，佐剂通过诱导某些细胞因子来指导亚型转换过程，这一发现有助于选择最有效的保护性抗体亚型用于疫苗接种预防疾病。
