树突状细胞在小儿哮喘发病机制中的作用

目的　探讨树突状细胞 (DC)在小儿哮喘发病中的可能作用及机制。方法　以Thomas法 ,采用粒 巨噬细胞集落刺激因子 ,白细胞介素 4 (IL 4 )和肿瘤坏死因子α(TNF α)联合培养诱导哮喘患儿外周血DC细胞 ,进而检测DC协同刺激分子B7 1(CD80 )、B7 2 (CD86)的表达 ,DC诱导自体T淋巴细胞的增殖反应 ,以及其分泌的IL 10、IL 12等水平的变化。结果　哮喘患儿外周血DC诱导自体T淋巴细胞增殖反应明显高于对照组 (cpm值分别为 115 6 0± 12 6和 6 5 39± 12 6 ,t =12 1 6 96 ) ,差异有非常显著意义 (P <0 0 1) ;其分泌IL 10水平 [( 3 6± 0 3) μg/L]明显低于对照组 [( 6 9± 0 8) μg/L],差异有非常显著意义 (t=2 0 6 0 8,P <0 0 1) ;分泌IL 12水平 [( 2 9 7± 8 4 )ng/L]也明显低于对照组 [( 4 5 2± 9 8)ng/L],差异有非常显著意义 (t=5 979,P <0 0 1) ;同时 ,哮喘患儿外周血人类白细胞抗原DR( 19 9± 1 3)和协同刺激分子B7 2 (CD86)的表达水平 ( 36 3± 14 0 )明显高于对照组( 10 6± 1 5和 2 4 7± 8 5 ) ,差异有非常显著意义 (t分别 =2 3 30 1和 3 314 ,P均 <0 0 1)。结论　DC可能通过诱导TH1/TH2细胞分化在小儿哮喘发作时起重要作用。其可能的机制系通过DC分泌的细胞因子而起作用。

Role of dendritic cells in the pathogenesis of asthma in children

Dendritic cells (DC) are very potent antigen-presenting cells (APC) with a unique ability to activate naive T cells to induce the differentiation of TH1/TH2. Monocytes can develop into DC in the presence of different cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. DCs are thought to play a key role in the initiation and maintenance of T cell immunity to inhaled antigens. While the density of DC within the bronchial mucosa is increased in asthma, there is little information currently available concerning the effects of DC in asthmatic children. OBJECTIVE: To investigate the role of dendritic cells in the pathogenesis of acute attack of asthma in children. METHODS: Thomas' method was adopted. The adherent precursors of DC were isolated from peripheral blood of asthmatic children in acute attack stage and healthy controls. The adherent cells were induced with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha) to DC in vitro. The expression of the surface molecules CD80, CD86, HLA-DR etc. on the DC was examined by fluorescent activated cell sorter (FACS). And the ability to secret IL-10, IL-12 and their potentials to stimulate the proliferative reaction of DC inductive self T- lymphocyte were observed. RESULTS: The results showed that in asthmatic children's acute attack stage, self T- lymphocyte proliferative reaction induced by DC was remarkably increased compared with normal control subjects (P < 0.01). At the same time, the asthmatic children in acute attack stage had remarkably decreased the ability to secret IL-10 compared with normal control subjects (P < 0.01), while the ability to secret IL-12 remarkably decreased compared with normal control subjects (P < 0.01); meanwhile, the HLA-DR and co-stimulating factor CD86(B(7-2)) expressed by DCs remarkably increased in the asthmatic children in acute attack stage compared with normal control subjects (P < 0.01). CONCLUSION: DC possibly plays a vital role in the immunological mechanism of asthma by means of inducing the differentiation of TH1/TH2, that is DC may be the key factor in initiating the airway allergic reaction and the possible mechanism may involve interleukins (especially IL-10 and IL-12, etc.) secreted by DCs.