Peng Ho Jen, Su Song Nan, Chang Zo Nan, Chao Pei Ling, Kuo Shu Wen, Tsai Lai Chen
Department of Medical Research, Veterans General Hospital-Taipei, Taipei 11217, Taiwan.
Vaccine. 2002 Mar 15;20(13-14):1761-8. doi: 10.1016/s0264-410x(02)00029-4.
DNA vaccines encoding low-molecular-weight allergens have been used to prevent IgE responses. A high-molecular-weight mite allergen Der f 11 that was hardly to be purified for immunotherapy was used to develop a DNA vaccine here. Vaccination of mice with plasmid DNA encoding Df11 (pDf11) induced Th1 responses characterized by IgG2a responses and spleen cell secretion of IFN-gamma. In contrast, sensitization with recombinant Der f 11 (rDf11) and alum induced Th2 responses characterized by IgE responses and spleen cell secretion of IL-4 and IL-5. Vaccination with pDf11 prevented the induction of IgE responses. Moreover, it could inhibit on-going IgE responses. The debate whether CD4+ or CD8+ T cells were the regulatory cells to inhibit IgE responses by DNA vaccination was also examined. First, sensitization of pDf11-vaccinated mice after depletion of CD8+ T cells still showed suppression of IgE responses. Secondly, adoptive transfer of either CD4- or CD8-depleted spleen cells from pDf11-vaccinated mice suppressed IgE responses. In conclusion, this is the first report to confirm the therapeutic effect of a DNA vaccine encoding a strong allergen on specific IgE responses. Both CD4+ and CD8+ T cells are crucial for the immunomodulation of IgE responses by pDf11.
编码低分子量变应原的DNA疫苗已被用于预防IgE反应。本文利用一种难以纯化用于免疫治疗的高分子量螨变应原Der f 11开发了一种DNA疫苗。用编码Df11的质粒DNA(pDf11)对小鼠进行疫苗接种可诱导以IgG2a反应和脾细胞分泌IFN-γ为特征的Th1反应。相比之下,用重组Der f 11(rDf11)和明矾致敏可诱导以IgE反应以及脾细胞分泌IL-4和IL-5为特征的Th2反应。用pDf11进行疫苗接种可预防IgE反应的诱导。此外,它还能抑制正在进行的IgE反应。本文还探讨了DNA疫苗接种抑制IgE反应的调节细胞是CD4+还是CD8+ T细胞这一争议问题。首先,在CD8+ T细胞耗竭后对pDf11接种的小鼠进行致敏,仍显示出对IgE反应的抑制作用。其次,将pDf11接种小鼠的CD4或CD8耗竭的脾细胞进行过继转移可抑制IgE反应。总之,这是第一份证实编码强变应原的DNA疫苗对特异性IgE反应具有治疗作用的报告。CD4+和CD8+ T细胞对pDf11对IgE反应的免疫调节都至关重要。