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目的：研究特异性免疫治疗（SIT）对哮喘小鼠自然杀伤T（NKT）细胞的影响。方法：24 只BALB/C 小鼠随机分为对照组（A 组）、哮喘模型组（B 组）、哮喘免疫治疗（SIT）组（C 组），各8 只。通过屋尘螨提取液（HDM）诱导建立哮喘小鼠模型并进行SIT 治疗。检测各组小鼠的气道反应性、支气管肺泡灌洗液(BAlF)细胞计数及分类、ELISA 检测IL-4、IFN-γ 以及应用流式细胞仪检测 NKT 细胞数目，通过RT-PCR 方法检测T-bet 和GATA-3mRNA 表达水平;HE 染色观察小鼠肺组织的改变。结果：与B 组相比，C 组气道反应性明显下降(P<0.01)；BALF 中细胞总数及嗜酸性粒细胞(EOS)数显著减少(P<0.01)；血清IL-4 分泌显著降低(P<0.01)， IFN-γ 显著升高(P<0.01)；NKT 细胞数及其成熟型比例明显升高(P<0.05)；T-betmRNA 表达水平明显升高(P<0.01)，且与NKT 细胞数及其成熟型比例呈正相关性，GATA-3mRNA 表达水平明显降低(P<0.05)，且与NKT 细胞数及其成熟型比例呈负相关性。B 组肺部管腔周围炎性细胞聚集，组织上皮损伤，组织水肿，而C 组肺部变应性炎症明显减轻。C 组其他各项指标接近A 组。结论：哮喘的发生可能与NKT 细胞失调相关，通过改变NKT 细胞数目及其成熟型比例来调节GATA-3 /T-bet 的表达可能是SIT 治疗哮喘的作用机制之一。

英文摘要:

Objective: To investigate the effects of specific immunotherapy on the NKT cells in house dust mite (HDM) extracts-sensitized murine mode. Methods: Twenty-four BALB/C mice were randomly divided into three groups （with 8 in each group）: control group（group A）,asthma group（group B）, SIT group（group C）. The model of asthma were sensitized and challenged by HDM extracts while SIT group were subcutaneously immunized by HDM extracts. Twenty-four hours after the challenge, airway hyperresponsiveness of mice, total cellular score and cell classification in bronchoalveolar lavage fluid （BALF）,the serum level of IL-4 were examined. IFN-γ was detected by ELISA, the number of NKT cells was determined by flow-cytometry, the expression of T-bet and GATA-3 mRNA was detected by RT-PCR, lung inflammation was detected by HE stain. Results: Compared with that in the group B, airway hyperresponsiveness in group C decreased （P＜0.01）.Specific immunotherapy significantly inhibit inflammation in mouse lung tissue pathological changes; Total cells and eosinophils (EOS) in BALF reduced significantly (P <0.01); Serum IL-4 was significantly lower (P <0.01); IFN-γ secretion was significantly higher (P <0.01); NKT cells number and the proportion of mature cells increased significantly (P <0.05); The level of T-bet mRNA expression increased significantly (P <0.01), and it was positively correlated with the number of NKT cells and its proportion of mature; The level of GATA-3mRNA expression were significantly lower (P <0.05), and it was negatively correlated with the number of NKT cells and its proportion of mature. The interstitial space surrounding the airway lumen was characterized by a densely mixed cellular infiltrate, epithelium tissue damage and tissue edema in group B, while lung inflammation of group C reduced considerably. Each test value of group C was substantially similar with that of group A. Conclusion: The occurrence of asthma may be associated with NKT cell dysfunction. By changing the number of NKT cells and its proportion of mature to regulate the GATA-3 / T-bet expression may be one of the mechanisms by which SIT was in the treatment of asthma.

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