Kildsgaard Jens, Brimnes Jens, Jacobi Henrik, Lund Kaare
Corporate Research, Chr. Hansen A/S, Hoersholm, Denmark.
Ann Allergy Asthma Immunol. 2007 Apr;98(4):366-72. doi: 10.1016/S1081-1206(10)60884-8.
Many studies have demonstrated immunologic changes induced by sublingual immunotherapy (SLIT), but the definitive mechanism of action needs further investigation.
To study the immunologic response induced by SLIT in sensitized mice.
Timothy grass (Phleum pratense)-sensitized mice received SLIT for 2, 4, or 6 weeks at 3 different concentrations, including a buffer control. Serum samples and washes of the lungs (bronchoalveolar lavage [BAL]) and the nasal passages (nasal lavage [NAL]) were analyzed for allergen-specific antibodies. T cells were isolated from the spleen and cervical lymph nodes for the analysis of proliferation and cytokine production.
Sublingual immunotherapy in sensitized mice resulted in a 30-fold increase in antigen specific IgA levels in BAL and NAL fluid compared with buffer-treated mice, whereas antigen specific IgE was undetectable in BAL and NAL fluid in animals treated with SLIT. Furthermore, IgA levels were proportional to the dose and duration of SLIT. Levels of specific IgA in serum correlated with levels in BAL and NAL fluid. Serum IgA levels were proportional to the duration of allergen exposure to the oral mucosa. Conversely, no changes in serum levels of IgE and IgG were induced by SLIT. Proliferation of T cells was increased in mice treated with SLIT compared with nontreated mice.
High levels of IgA in serum and in BAL and NAL fluid of mice treated with SLIT demonstrate that SLIT induces a mucosal, nonallergic response in sensitized mice.
许多研究已证实舌下免疫疗法(SLIT)可引发免疫变化,但确切的作用机制仍需进一步研究。
研究SLIT在致敏小鼠中诱导的免疫反应。
用梯牧草(Phleum pratense)致敏的小鼠,以3种不同浓度接受SLIT治疗2、4或6周,包括一个缓冲液对照组。分析血清样本以及肺(支气管肺泡灌洗[BAL])和鼻腔(鼻腔灌洗[NAL])的冲洗液中的过敏原特异性抗体。从脾脏和颈部淋巴结分离T细胞,用于分析增殖和细胞因子产生情况。
与缓冲液处理的小鼠相比,致敏小鼠的舌下免疫疗法使BAL和NAL液中抗原特异性IgA水平增加了30倍,而在接受SLIT治疗的动物的BAL和NAL液中未检测到抗原特异性IgE。此外,IgA水平与SLIT的剂量和持续时间成正比。血清中特异性IgA水平与BAL和NAL液中的水平相关。血清IgA水平与过敏原暴露于口腔黏膜的持续时间成正比。相反,SLIT未诱导血清中IgE和IgG水平发生变化。与未处理的小鼠相比,接受SLIT治疗的小鼠T细胞增殖增加。
接受SLIT治疗的小鼠血清以及BAL和NAL液中高水平的IgA表明,SLIT在致敏小鼠中诱导了一种黏膜非过敏反应。