舌下草花粉免疫治疗与舌下调 Foxp3 表达细胞的增加以及过敏原特异性 IgG4、IgA 和血清抑制活性相关，该抑制活性可阻止 IgE 促进过敏原与 B 细胞结合。

Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells.

机构信息

National Heart and Lung Institute, Imperial College London, UK.

出版信息

Clin Exp Allergy. 2010 Apr;40(4):598-606. doi: 10.1111/j.1365-2222.2010.03462.x. Epub 2010 Feb 22.

DOI:10.1111/j.1365-2222.2010.03462.x

PMID:20184605

Abstract

BACKGROUND

The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT).

OBJECTIVES

To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB).

METHODS

Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebo-treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-beta mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT.

RESULTS

Foxp3(+) cells were increased in the oral epithelium of SLIT- vs. placebo-treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT- compared with placebo-treated atopics (P=0.1 for both). IgG(1) and IgG(4) were increased following SLIT (P<0.001). Peak seasonal IgA(1) and IgA(2) were increased during SLIT (P<0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics.

CONCLUSIONS

SLIT with grass pollen extract is associated with increased Foxp3(+) cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

摘要

背景

舌下免疫疗法（SLIT）的机制不如皮下免疫疗法（SCIT）那么清楚。

目的

确定草花粉 SLIT 对口腔黏膜免疫细胞、局部调节细胞因子、血清变应原特异性抗体亚类和 B 细胞 IgE 促进变应原结合（IgE-FAB）的影响。

方法

通过免疫荧光显微镜检查舌下黏膜活检组织中髓样树突状细胞（mDC）（CD1c）、浆细胞样树突状细胞（CD303）、肥大细胞（AA1）、T 细胞（CD3）和 Foxp3 的表达。通过原位杂交鉴定 IL-10 和 TGF-β mRNA 的表达。在 SLIT 之前、期间和完成后测量过敏原特异性 IgG 和 IgA 亚类以及血清抑制结合过敏原-IgE 复合物至 B 细胞的活性（IgE-FAB）。

结果

与安慰剂治疗的特应性患者相比，SLIT 治疗的特应性患者的口腔上皮中 Foxp3(+)细胞增加（P=0.04）。与正常对照组相比，安慰剂治疗的特应性患者而非 SLIT 治疗的特应性患者的粘膜下 mDC 数量更多（P=0.05）。与安慰剂治疗的特应性患者相比，SLIT 治疗的特应性患者粘膜下肥大细胞较少，上皮 T 细胞较多（两者均为 P=0.1）。SLIT 后 IgG(1)和 IgG(4)增加（P<0.001）。SLIT 期间季节性 IgA(1)和 IgA(2)峰值增加（P<0.05）。SLIT 治疗的特应性患者中，血清 IgE-FAB 抑制活性呈时间依赖性增加。