Regulation of allergic inflammation by the induction T cell anergy

通过快速免疫疗法(R1)的治疗，我们发现Th2细胞在启动Ri后的早期就对特定的过敏原诱导了对特定过敏原的无应答。为了阐明这种无应答的机制，我们在体外检测了T细胞对不同剂量的过敏原的反应。从对尘螨和猫变应原敏感的哮喘患者中分离出PBMC。用0.01、0.1、1、10、100、500µg/ml的粉尘变应原刺激PBMC 7天。低剂量的过敏原(0.01 mg/ml)几乎不能诱导T细胞的增殖和大量IL-4的产生。经二次培养后，T细胞增殖并产生大量的IL-4和IL-5(Th2型细胞因子)。用高剂量变应原(500 mg/ml)刺激PBMC，第一次培养后T细胞增殖旺盛，第二次培养后T细胞不再增殖。它们不产生任何细胞因子IL-4、IL-5、II-10(Th2)和干扰素-γ(Th1)。不同浓度的Fel Di对Feld1特异性Th2细胞克隆也有类似的反应，Fel Di是CAT的主要变应原。加入IL-2后可恢复应答，这是T细胞无能的特点。这些无能细胞在无能诱导之前，通过添加IL-2，以类似的方式对CAT过敏原的主要表位PC1或PC2做出反应。这些数据表明，高浓度的过敏原可以诱导Th2细胞无能。这可能是急诊免疫治疗后Th2细胞无应答的机制之一。

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.