Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Department of Immunology, Allergology and Immunotoxicology, Hannover, Germany.
Immunobiology. 2011 Jan-Feb;216(1-2):110-7. doi: 10.1016/j.imbio.2010.05.003. Epub 2010 May 8.
According to the hygiene hypothesis, triggering the immune system with microbial components during childhood balances the inherent Th2 bias. In contrast, specific immunotherapy involves exposure of the patient to the allergen in order to achieve desensitization to subsequent contact. In a human in vitro allergy model the potential of the TLR2/6 agonist BPPcysMPEG to modulate antigen presenting cells and allergen-specific immune responses was evaluated. Specific immunomodulation via co-administration of the allergen and BPPcysMPEG enhanced expression of co-stimulatory molecules on DC and increased secretion of the proinflammatory cytokine TNF-α. Acting as an adjuvant, BPPcysMPEG elevated allergen-specific immune responses in co-culture with autologous lymphocytes. Although administration of BPPcysMPEG alone enhanced expression of co-stimulatory molecules on DC, proliferation of autologous lymphocytes was not induced. Based on this finding, the potential of BPPcysMPEG to reduce allergic airway inflammation by preventive modulation of the innate immune system via TLR2/6 agonization was investigated in mice. Local administration of BPPcysMPEG altered cellular influx and cell composition in BAL fluid. Furthermore, the Th2-associated cytokines IL-4 and IL-5 were diminished. Allergen-specific restimulation of cells from mediastinal lymph nodes and splenocytes suggested an alteration of immune responses. The treatment with BPPcysMPEG induced a Th1-dominated cytokine milieu in mediastinal lymph nodes, while allergen-specific immune responses in splenocytes were diminished. The co-administration of allergen and BPPcysMPEG reduced cytokine secretion upon restimulation in mediastinal lymph nodes and splenocytes. From these data we conclude that BPPcysMPEG was able to influence the immune system with regard to subsequent allergen contact by TLR2/6 agonization.
根据卫生假说，在儿童期用微生物成分触发免疫系统可以平衡固有 Th2 偏向。相比之下，特异性免疫治疗涉及使患者暴露于过敏原，以实现对随后接触的脱敏。在人类体外过敏模型中，评估了 TLR2/6 激动剂 BPPcysMPEG 调节抗原呈递细胞和过敏原特异性免疫反应的潜力。通过共给予过敏原和 BPPcysMPEG 进行特异性免疫调节，增强了 DC 上共刺激分子的表达，并增加了促炎细胞因子 TNF-α的分泌。作为佐剂，BPPcysMPEG 在与自体淋巴细胞共培养时增强了过敏原特异性免疫反应。尽管单独给予 BPPcysMPEG 增强了 DC 上共刺激分子的表达，但并未诱导自体淋巴细胞的增殖。基于这一发现，通过 TLR2/6 激动作用预防调节固有免疫系统，研究了 BPPcysMPEG 降低过敏性气道炎症的潜力。BPPcysMPEG 的局部给药改变了 BAL 液中的细胞流入和细胞组成。此外，Th2 相关细胞因子 IL-4 和 IL-5 减少。来自纵隔淋巴结和脾细胞的过敏原特异性再刺激表明免疫反应发生改变。BPPcysMPEG 治疗诱导了纵隔淋巴结中 Th1 占主导地位的细胞因子环境，而脾细胞中的过敏原特异性免疫反应减少。共给予过敏原和 BPPcysMPEG 减少了纵隔淋巴结和脾细胞中再刺激时细胞因子的分泌。从这些数据中，我们得出结论，BPPcysMPEG 能够通过 TLR2/6 激动作用影响免疫系统，从而影响随后与过敏原的接触。
