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Expansion of circulating Foxp3+)D25bright CD4+ T cells during specific venom immunotherapy.

机译:在特定毒液免疫治疗过程中循环Foxp3 +)D25bright CD4 + T细胞的扩增。

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BACKGROUND: Venom immunotherapy (VIT) induces long-lasting immune tolerance to hymenoptera venom antigens, but the underlying mechanisms are not yet clarified. Regulatory T cells are thought to play an important role in allergic diseases and tolerance induction during specific immunotherapy. AIM: Characterize longitudinally the impact of VIT on the pool of circulating regulatory T cells. METHODS: Fourteen hymenoptera venom-allergic patients with severe reactions (grades III-IV) were studied before, 6 and 12 months after starting ultra-rush VIT. Freshly isolated peripheral blood mononuclear cells were surface stained with a panel of markers of T cell differentiation and intracellularly for CTLA-4 and Foxp3 and analysed by flow cytometry. foxp3 mRNA was quantified by real-time PCR. VIT responses were assessed by measuring specific IgG4 and IgE levels. Eleven individuals with no history of insect venom allergy were studied as controls. RESULTS: VIT induces a significant progressive increase in both the proportion and the absolute numbers of regulatory T cells defined as CD25bright and/or Foxp3+ CD4+ T cells. These changes are not related to alterations in the expression of activation markers or imbalances in the naive/memory T cell compartments. foxp3 mRNA levels also increased significantly during VIT. Of note, the increase in circulating regulatory T cell counts significantly correlates with the venom-specific IgG4/IgE ratio shift. CONCLUSION: VIT is associated with a progressive expansion of circulating regulatory T cells, supporting a role for these cells in tolerance induction.
机译:背景:毒液免疫疗法(VIT)诱导对膜翅目毒液抗原的持久免疫耐受,但其潜在机制尚未阐明。人们认为,调节性T细胞在特异性免疫治疗过程中的过敏性疾病和耐受性诱导中起重要作用。目的:纵向表征VIT对循环调节性T细胞池的影响。方法:在开始超急诊VIT之前,6个月和12个月后,对14例严重反应的膜翅目蛇毒过敏患者进行了研究。用一组T细胞分化标志物对新鲜分离的外周血单核细胞进行表面染色,并在细胞内对CTLA-4和Foxp3进行染色,并通过流式细胞术进行分析。通过实时PCR定量foxp3 mRNA。通过测量特异性IgG4和IgE水平评估VIT反应。研究了没有昆虫毒液过敏史的11个人作为对照。结果:VIT诱导被定义为CD25bright和/或Foxp3 + CD4 + T细胞的调节性T细胞的比例和绝对数量显着增加。这些变化与激活标志物表达的改变或幼稚/记忆T细胞区室的失衡无关。在VIT期间foxp3 mRNA水平也显着增加。值得注意的是,循环调节性T细胞计数的增加与毒液特异性IgG4 / IgE比值变化显着相关。结论:VIT与循环调节性T细胞的逐步扩增有关,支持这些细胞在耐受性诱导中的作用。

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