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T lymphocytes expressing CCR3 are increased in allergic rhinitis compared with non-allergic controls and following allergen immunotherapy.

机译:与非过敏性对照相比,在过敏原免疫治疗后,表达CCR3的T淋巴细胞在过敏性鼻炎中增加。

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BACKGROUND: In T cell-associated allergic inflammation, homing of T-helper 2 (Th2) effector cells to mucosal sites may be influenced by chemokine receptor expression. Previous studies have identified CCR3 and CCR4 as putative markers of Th2 cells and CCR5 and CXCR3 as markers of Th1 cells. The aim of this study was to assess differential chemokine receptor expression from symptomatic atopic grass pollen-sensitive subjects, compared with patients on high-dose allergen injection immunotherapy (IT) and healthy controls. METHODS: We examined chemokine receptor expression (CCR1-7 and CXCR1-4) by flow cytometry of peripheral blood CD4+ and CD8+ T cells. We also depleted peripheral blood mononuclear cell (PBMC) populations of CCR3+ CD4+ cells by magnetic bead separation and cells were stimulated with grass pollen allergen for 6 days. Cytokine production was measured by enzyme-linked immunosorbent assay. RESULTS: On freshly isolated PBMC, atopic individuals exhibited increased numbers of CCR3+ CD4+ cells compared with normal controls (P < 0.01). CCR3 expression in IT patients was reduced compared with matched atopic rhinitic controls (P < 0.05) and comparable with that observed in normal subjects. Depletion of CCR3+ CD4+ cells from allergen-stimulated PBMC cultures resulted in decreased interleukin (IL)-5 production compared with whole CD4+ populations (P < 0.05). Freshly isolated CCR3+ CD4+ cells have significantly higher intracellular IL-4 and lower IFN-gamma levels than CCR3- CD4+ cells. CD4+ T cells cultured from both peripheral cells and nasal biopsies demonstrated increased expression of CCR3 in the presence of IL-4 (P < 0.05). CONCLUSION: CCR3+ CD4+ T cells are increased in allergic rhinitis, are reduced by allergen IT, have a Th2 phenotype and contribute to allergen-specific responses. Strategies against CCR3+ T cells may be effective in human allergic diseases.
机译:背景:在T细胞相关的过敏性炎症中,趋化因子受体的表达可能会影响T辅助2(Th2)效应细胞向粘膜部位的归巢。先前的研究已将CCR3和CCR4鉴定为Th2细胞的推定标记,并将CCR5和CXCR3鉴定为Th1细胞的标记。这项研究的目的是评估与有症状的过敏性草花粉敏感受试者的趋化因子受体表达的差异,并与接受大剂量过敏原注射免疫疗法(IT)和健康对照的患者进行比较。方法:我们通过外周血CD4 +和CD8 + T细胞的流式细胞术检查了趋化因子受体的表达(CCR1-7和CXCR1-4)。我们还通过磁珠分离消耗了CCR3 + CD4 +细胞的外周血单核细胞(PBMC)群体,并用草花粉过敏原刺激了细胞6天。通过酶联免疫吸附测定法测量细胞因子的产生。结果:在新鲜分离的PBMC上,特应性个体的CCR3 + CD4 +细胞数量比正常对照组增加(P <0.01)。与匹配的特应性鼻炎对照组相比,IT患者的CCR3表达降低(P <0.05),与正常受试者的观察结果相当。与整个CD4 +群体相比,变应原刺激的PBMC培养物中CCR3 + CD4 +细胞的耗竭导致白细胞介素(IL)-5产量降低(P <0.05)。新鲜分离的CCR3 + CD4 +细胞比CCR3- CD4 +细胞具有更高的细胞内IL-4水平和更低的IFN-γ水平。从外周细胞和鼻活检组织培养的CD4 + T细胞在IL-4存在下显示CCR3表达增加(P <0.05)。结论:变应性鼻炎中CCR3 + CD4 + T细胞增加,变应原IT减少,具有Th2表型,并有助于变应原特异性反应。针对CCR3 + T细胞的策略可能对人类过敏性疾病有效。

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