Suppression of the immunologic response to peanut during immunotherapy is often transient
Suppression of the immunologic response to peanut during immunotherapy is often transient
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DOI：
10.1016/j.jaci.2014.11.010
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发表时间：
2015-05-01
影响因子：
14.2
通讯作者：
Frischmeyer-Guerrerio, Pamela A.
中科院分区：
文献类型：
--
作者：
Gorelik, Mark;Narisety, Satya D.;Frischmeyer-Guerrerio, Pamela A.
背景资料：研究表明，口服免疫疗法（OIT）和舌下免疫疗法（SLIT）对食物过敏有希望，然而，这些疗法背后的免疫学机制还没有很好地理解。目的：我们试图深入了解免疫疗法期间花生免疫应答抑制的机制和持续时间。在花生OIT和SLIT的安慰剂对照试验期间，在基线和多个时间点从受试者获得血液。免疫学结果包括使用自动荧光测定法测量自发和刺激的嗜碱性粒细胞活性（组胺）和流式细胞术（活化标志物和IL-4），通过使用多重技术测量树突状细胞（DC）-T细胞共培养物中变应原诱导的细胞因子表达，以及通过使用流式细胞术测量DC上的MHC II和共刺激分子表达。在剂量递增期间和维持给药6个月后，自发和过敏原诱导的嗜碱性粒细胞反应性（组胺释放、CD 63表达和IL-4产生）受到抑制。在免疫治疗期间，花生和尘螨诱导的T（H）2细胞因子表达在DC-T细胞共培养物中减少。这与DC上的CD 40、HLA-DR和CD 86表达水平降低以及CD 80表达增加有关。这些作用在来自接受OIT的受试者的骨髓DC-T细胞共培养物中最为显著。许多标志物的免疫抑制逆转后退出immunotherapy，并在某些情况下，在正在进行的maintenance therapy.Conclusion：OIT和SLIT花生过敏诱导快速抑制嗜碱性粒细胞效应功能，DC激活，和TH 2细胞因子反应在免疫治疗的初始阶段，在抗原非特异性的方式。虽然有一些个体间的差异，在许多患者的抑制似乎是暂时的。
Background: Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood.Objective: We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy.Methods: Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)-T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry.Results: Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut-and dust mite-induced expression of T(H)2 cytokines was reduced in DC-T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC-T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy.Conclusion: OITand SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and TH2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.