Regulation of allergic inflammation by the induction T cell anergy

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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.