Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BMC Immunol. 2012 Jul 6;13:34. doi: 10.1186/1471-2172-13-34.
Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.
In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.
Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.
抗原特异性免疫疗法（SIT）已广泛应用于治疗哮喘等过敏性疾病。然而，这种治疗方法在治疗过程中可能会引起一系列过敏不良反应。肽免疫疗法（PIT）被探索用来克服这些缺点。我们证实，多种抗原肽（MAPs）不会引起自身免疫反应，这导致人们推测 MAPs 干预可以缓解过敏气道炎症而不会引起不良反应。
在这项研究中，皮下注射合成的 OVA323-339MAP 八聚体到卵清蛋白（OVA）致敏和激发的 Balb/c 小鼠中，观察其对过敏性气道炎症、Th2 免疫反应和免疫调节功能的影响。结果证实，OVA 致敏和激发导致明显的气管周围炎症、细胞浸润和强烈的 Th2 反应。在气道炎症小鼠模型中，OVA323-339MAP 八聚体治疗增加了外周血、纵隔引流淋巴结和脾脏中的 CD4+CD25+Foxp3+调节性 T（Treg）细胞及其调节功能。此外，OVA323-339MAP 增加了支气管肺泡灌洗液（BALF）中的白细胞介素 10（IL-10）水平；上调了肺组织中 IL-10、膜结合 TGF-β1 和 Foxp3 的表达；并上调了 Treg 细胞表面的程序性死亡-1（PD-1）和细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）。这些结果与 BALF 中炎症细胞如嗜酸性粒细胞和淋巴细胞浸润减少以及 OVA 特异性免疫球蛋白 E（sIgE）水平降低有关。然而，在相同的动物模型中，OVA323-339 肽单体没有表现出上述任何作用。
我们的研究表明，OVA323-339MAP 通过体内调节 Th1/Th2 反应平衡对过敏性气道炎症的小鼠具有显著的治疗作用。
