Lee B K, Yoo Y G, Lee W Y, Hong C S, Park J K, Ro J Y
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 2001 Feb;42(1):91-105. doi: 10.3349/ymj.2001.42.1.91.
For those with allergy, vaccination with a specific allergen has often been used as a major therapeutic measure. However, the universal application of this technique in clinics have been restricted due to its low success rates and the risk of active systemic anaphylactic shock (ASAS). In this regard, we constructed a fusion protein (OVA-DT), ovalbumin (OVA) fused with diphtheria toxin protein (DT), which may exert a specific cytotoxicity to cells bearing OVA-specific IgE. Its therapeutic effect was evaluated in mice (BALB/c) sensitized with OVA (Os-mice). OVA challenges to the OVA-sensitized mice (Os-mice) caused ASAS to death within 30 min, but OVA-DT treatment afforded mice complete protection. When OVA-DT was treated to the Os-mice, none showed the signs of ASAS when re-challenged 48 h after the treatment. OVA-DT itself was not found to be toxic or allergenic in normal mice. The effect of OVA-DT on the biological functions of mast cells was also studied. Binding of OVA-DT to OVA-specific IgE bearing mast cells and the inhibition of histamine release from these cells were observed. In addition, OVA-DT treatment inhibited the proliferation of OVA-specific B cells in mice. In Os-mice treated with OVA-DT, levels of anti-OVA IgG2a in serum and the production of IFN-gamma by splenic lymphocytes were found to increase, but the production of IL-4 by these cells decreased. Re-direction of cytokine profiles from OVA-specific Th2 to OVA-specific Thl is suggested. These results indicate that OVA-DT can protect Os-mice from ASAS due to OVA challenge, because it inactivates OVA-specific IgE-expressing cells, including mast cells and B cells.
对于过敏患者，使用特定过敏原进行疫苗接种常常被用作一种主要的治疗手段。然而，由于该技术成功率较低且存在发生全身性过敏性休克（ASAS）的风险，其在临床上的广泛应用受到了限制。在这方面，我们构建了一种融合蛋白（OVA-DT），即卵清蛋白（OVA）与白喉毒素蛋白（DT）融合而成，它可能对携带OVA特异性IgE的细胞发挥特异性细胞毒性作用。我们在经OVA致敏的小鼠（Os小鼠，BALB/c）中评估了其治疗效果。对OVA致敏小鼠（Os小鼠）进行OVA激发会导致在30分钟内发生ASAS致死，但OVA-DT治疗为小鼠提供了完全保护。当对Os小鼠给予OVA-DT治疗后，在治疗后48小时再次激发时，没有一只小鼠出现ASAS的迹象。在正常小鼠中未发现OVA-DT本身具有毒性或致敏性。我们还研究了OVA-DT对肥大细胞生物学功能的影响。观察到OVA-DT与携带OVA特异性IgE的肥大细胞结合，并抑制这些细胞释放组胺。此外，OVA-DT治疗抑制了小鼠中OVA特异性B细胞的增殖。在用OVA-DT治疗的Os小鼠中，发现血清中抗OVA IgG2a水平以及脾淋巴细胞产生的IFN-γ增加，但这些细胞产生的IL-4减少。提示细胞因子谱从OVA特异性Th2向OVA特异性Th1发生了重定向。这些结果表明，OVA-DT可以保护Os小鼠免受OVA激发引起的ASAS，因为它使包括肥大细胞和B细胞在内的表达OVA特异性IgE的细胞失活。
