Regulation of allergic inflammation by the induction T cell anergy

通过快速免疫疗法（R1）的治疗，包括在几天内增加过敏原的剂量以达到维持剂量，我们发现在开始RI后早期诱导Th2细胞对特定过敏原的无反应性。为了阐明这种无反应性的机制，我们在体外检测了T细胞对不同剂量过敏原的反应。将PBMC与哮喘、螨、猫过敏原敏感患者分离。分别用0.01、0.1、1、10、100、500马克/毫升的螨虫过敏原刺激PBMC 7天。低剂量的变应原（0.01mg/ml）诱导T细胞增殖少，IL-4产生显著。这些细胞经过二次培养后，T细胞增殖并产生大量的IL-4和IL-5 （Th2细胞因子）。当高剂量（500mg/ml）的过敏原刺激PBMC时，T细胞在第一次培养后增殖旺盛，而在第二次培养后增殖不明显。它们不产生任何细胞因子，IL-4、IL-5、II-10 （Th2）和ifn - γ (Th1)细胞因子。不同浓度猫主要过敏原Fel - dI对Feld - 1特异性Th2细胞克隆也有类似的反应。通过添加IL-2恢复反应性，这是T细胞能量的特征。这些无能细胞通过添加IL-2对猫过敏原PC1或PC2的主要表位作出反应，在能量诱导之前以类似的方式。这些数据表明，高浓度的过敏原可以诱导Th2细胞产生能量。这可能是快速免疫治疗后Th2细胞无反应的机制之一。

By the treatment with rush immunotherapy (R1) , which involves incremental dosing with an allergen to reach a maintenance dose within several days, we found that Th2 cell unresponsiveness to specific allergen was induced in early after starting RI.In order to clarify the mechanism of this unresponsiveness, T cell responses to various dose of allergen were examined in vitro. PBMC were separated from patients with asthma, sensitive to mite and cat allergen. PBMC were stimulated with 0.01,0.1,1,10,100,500mug/ml of mite allergen for 7 days. Low dose of allergen (0.01mg/ml) induce little T cell proliferation and significant amounts of IL-4 production. After secondary culture of these cells, T cell proliferated and produced large amounts of IL-4 and IL-5 (Th2 cytokines). When PBMC were stimulated with high dose of allergen (500mg/ml), T cells proliferate vigorously after first culture but did not proliferate after secondary culture. They did not produce any cytokine, IL-4, IL-5, II-10 (Th2), and IFN-gamma(Th1) cytokine. The similar response was also observed in Feld 1-specific Th2 cell clones by various concentration Fel dI,major cat allergen. The responsiveness was recovered by the addition of IL-2, which is characteristics of T cell anergy. These anergic cells respond major epitopes of cat allergen, PC1 or PC2, by the addition of IL-2, in the similar way before anergy induction. These data indicate that high concentration of allergen can induce anergy in Th2 cells. This might be one of the mechanisms of Th2 cell unresponsiveness after rush immunotherapy.