Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy
Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy
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DOI：
10.1111/all.13436
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发表时间：
2018-09-01
期刊：
影响因子：
12.4
通讯作者：
Okamoto, Y.
中科院分区：
文献类型：
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作者：
Ihara, F.;Sakurai, D.;Okamoto, Y.
背景尽管众所周知 Th2 细胞在包括过敏性鼻炎 (AR) 在内的过敏性疾病中发挥重要作用，但诱导和维持 AR 发病机制的因素仍不清楚。最近舌下免疫疗法 (SLIT) 的发展有望改变 AR 的潜在发病机制。然而，哪些 Th2 细胞亚群在房尘螨诱导的 AR (HDM-AR) 中起重要作用、SLIT 对致病性 Th2 细胞的影响以及 Th2 细胞亚群与 SLIT 功效的关系尚未阐明。 方法使用流式细胞术评估 89 例外周血单核细胞 (PBMC) 中 HDM 反应性 T 细胞亚群的细胞因子产生和频率。 参加 HDM 片剂 SLIT 安慰剂对照研究的 HDM-AR 患者（安慰剂 [n=43] 和 HDM 300 IR [n=46]）。所有患者均在治疗前和 52 周研究结束时提供样本作为基线。 PBMCs在与HDM提取物培养前用CellTrace Violet (CTV)染色，检测到HDM反应性T细胞为CTV减少的增殖细胞。结果HDM反应性IL-5(+)IL-13(+)CD27(-)CD161(+)CD4(+)细胞和ST2(+)CD45RO(+)CD4(+)细胞 在每位 HDM-AR 患者的外周血中观察到；在用活性药片治疗的组中，这些细胞在 SLIT 后显着减少。 HDM反应性ST2(+)CD45RO(+)CD4(+)细胞在主动应答者中显着较低。 结论过敏原反应性ST2(+)CD45RO(+)CD4(+)细胞或与IL-5(+)IL-13(+)CD27(-)CD161(+)CD4(+)细胞组合的细胞可能作为SLIT治疗成功的标志物。这些细胞可能作为致病性记忆 Th2 细胞在 AR 的发病机制中发挥着至关重要的作用。
BackgroundAlthough Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified.MethodsThe cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo [n=43] and HDM 300 IR [n=46]) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV.ResultsHDM-reactive IL-5(+)IL-13(+)CD27(-)CD161(+)CD4(+) cells and ST2(+)CD45RO(+)CD4(+) cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2(+)CD45RO(+)CD4(+) cells were significantly lower in active-responders.ConclusionAllergen-reactive ST2(+)CD45RO(+)CD4(+) cells or those combined with IL-5(+)IL-13(+)CD27(-)CD161(+)CD4(+) cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.