Shirinbak Soheila, Taher Yousef A, Maazi Hadi, Gras Renée, van Esch Betty C A M, Henricks Paul A J, Samsom Janneke N, Verbeek J Sjef, Lambrecht Bart N, van Oosterhout Antoon J M, Nawijn Martijn C
Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, Groningen Research Institute for Asthma and COPD Research, University Medical Center Groningen, University of Groningen, Groningen;
J Immunol. 2010 Oct 1;185(7):3857-65. doi: 10.4049/jimmunol.0903909. Epub 2010 Aug 27.
Allergen-specific immunotherapy (IT) uniquely renders long-term relief from allergic symptoms and is associated with elevated serum levels of allergen-specific IgG and IgA. The allergen-specific IgG response induced by IT treatment was shown to be critical for suppression of the immediate phase of the allergic response in mice, and this suppression was partially dependent on signaling through FcγRIIB. To investigate the relevance of the allergen-specific IgG responses for suppression of the Th2-driven late-phase allergic response, we performed IT in a mouse model of allergic asthma in the absence of FcγRIIB or FcγRI/FcγRIII signaling. We found that suppression of Th2 cell activity, allergic inflammation, and allergen-specific IgE responses is independent of FcγRIIB and FcγRI/FcγRIII signaling. Moreover, we show that the IT-induced allergen-specific systemic IgG or IgA responses and B cell function are dispensable for suppression of the late-phase allergic response by IT treatment. Finally, we found that the secretory mucosal IgA response also is not required for suppression of the Th2-driven allergic inflammation by IT. These data are in contrast to the suppression of the immediate phase of the allergic response, which is critically dependent on the induced allergen-specific serum IgG response. Hence, IT-induced suppression of the immediate and late phases of the allergic response is governed by divergent and independent mechanisms. Our data show that the IT-induced suppression of the Th2 cell-dependent late-phase allergic response is independent of the allergen-specific IgG and IgA responses that are associated with IT treatment.
变应原特异性免疫疗法（IT）能独特地长期缓解过敏症状，并与变应原特异性IgG和IgA血清水平升高相关。IT治疗诱导的变应原特异性IgG反应对抑制小鼠过敏反应的速发相至关重要，且这种抑制部分依赖于通过FcγRIIB的信号传导。为了研究变应原特异性IgG反应对抑制Th2驱动的迟发相过敏反应的相关性，我们在缺乏FcγRIIB或FcγRI/FcγRIII信号传导的过敏性哮喘小鼠模型中进行了IT。我们发现，Th2细胞活性、过敏性炎症和变应原特异性IgE反应的抑制不依赖于FcγRIIB和FcγRI/FcγRIII信号传导。此外，我们表明，IT诱导的变应原特异性全身IgG或IgA反应以及B细胞功能对于IT治疗抑制迟发相过敏反应是可有可无的。最后，我们发现分泌性黏膜IgA反应对于IT抑制Th2驱动的过敏性炎症也不是必需的。这些数据与过敏反应速发相的抑制形成对比，速发相的抑制严重依赖于诱导的变应原特异性血清IgG反应。因此，IT诱导的过敏反应速发相和迟发相的抑制由不同且独立的机制控制。我们的数据表明，IT诱导的对Th2细胞依赖性迟发相过敏反应的抑制独立于与IT治疗相关的变应原特异性IgG和IgA反应。
