Immunomodulation and Tolerance Group, National Heart and Lung Institute, Imperial College London, London, UK.
Allergy. 2015 Feb;70(2):171-9. doi: 10.1111/all.12543.
Several studies have demonstrated the time course of inflammatory mediators in nasal fluids following nasal allergen challenge (NAC), whereas the effects of NAC on cells in the periphery are unknown. We examined the time course of effector cell markers (for basophils, dendritic cells and T cells) in peripheral blood after nasal grass pollen allergen challenge.
Twelve participants with seasonal allergic rhinitis underwent a control (diluent) challenge followed by NAC after an interval of 14 days. Nasal symptoms and peak nasal inspiratory flow (PNIF) were recorded along with peripheral basophil, T-cell and dendritic cell responses (flow cytometry), T-cell proliferative responses (thymidine incorporation), and cytokine expression (FluoroSpot assay).
Robust increases in nasal symptoms and decreases in PNIF were observed during the early (0-1 h) response and modest significant changes during the late (1-24 h) response. Sequential peaks in peripheral blood basophil activation markers were observed (CD107a at 3 h, CD63 at 6 h, and CD203c(bright) at 24 h). T effector/memory cells (CD4(+) CD25(lo) ) were increased at 6 h and accompanied by increases in CD80(+) and CD86(+) plasmacytoid dendritic cells (pDCs). Ex vivo grass antigen-driven T-cell proliferative responses and the frequency of IL-4(+) CD4(+) T cells were significantly increased at 6 h after NAC when compared to the control day.
Basophil, T-cell, and dendritic cell activation increased the frequency of allergen-driven IL-4(+) CD4(+) T cells, and T-cell proliferative responses are detectable in the periphery after NAC. These data confirm systemic cellular activation following a local nasal provocation.
几项研究已经证明了鼻过敏原挑战(NAC)后鼻液中炎症介质的时程,而 NAC 对周围细胞的影响尚不清楚。我们检查了鼻草花粉过敏原挑战后外周血效应细胞标志物(嗜碱性粒细胞、树突状细胞和 T 细胞)的时间过程。
12 名季节性过敏性鼻炎患者接受了对照(稀释剂)挑战,14 天后进行 NAC。记录鼻症状和最大鼻吸气流量(PNIF),以及外周嗜碱性粒细胞、T 细胞和树突状细胞反应(流式细胞术)、T 细胞增殖反应(胸苷掺入)和细胞因子表达(FluoroSpot 测定)。
在早期(0-1 小时)反应中观察到鼻症状明显增加和 PNIF 下降,在晚期(1-24 小时)反应中观察到适度显著变化。外周血嗜碱性粒细胞激活标志物呈顺序性峰值(CD107a 在 3 小时,CD63 在 6 小时,CD203c(明亮)在 24 小时)。T 效应/记忆细胞(CD4(+)CD25(lo))在 6 小时增加,并伴有 CD80(+)和 CD86(+)浆细胞样树突状细胞(pDC)增加。与对照日相比,NAC 后 6 小时,草抗原驱动的 T 细胞增殖反应和 IL-4(+)CD4(+)T 细胞的频率显著增加。
嗜碱性粒细胞、T 细胞和树突状细胞的激活增加了过敏原驱动的 IL-4(+)CD4(+)T 细胞的频率,并且 NAC 后在外周可检测到 T 细胞增殖反应。这些数据证实了局部鼻激发后全身细胞激活。