Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice
Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice
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DOI：
10.1183/09031936.05.00021304
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发表时间：
2005-04-01
影响因子：
24.3
通讯作者：
Higaki, J
中科院分区：
文献类型：
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作者：
Irifune, K;Yokoyama, A;Higaki, J
T辅助细胞1型（Th 1）细胞已被假定具有重要的作用，在保护性免疫对过敏性疾病。然而，最近的研究表明，极化的Th 1细胞在小鼠哮喘模型中对气道反应性和嗜酸性粒细胞炎症的影响相互矛盾。本研究探讨了过继转移已建立的Th 1细胞克隆对小鼠特应性哮喘模型的影响。小鼠（BALB/c）用卵清蛋白（OVA）致敏，并用雾化的OVA（5%，20分钟）攻击5天。就在开始第一次挑战之前，将Thl克隆（5 X 10（6.）体（-1））或单独的PBS通过尾静脉注射。在评估气道对乙酰甲胆碱的反应性后，获得支气管肺泡灌洗液（BALF）。组织学检查，包括形态计量学分析，细胞因子在BALF中的测量和肺趋化因子的北方印迹法，也进行了。连续转移的Th 1克隆显示显着增加的细胞总数，而显着减少嗜酸性粒细胞被发现在BALF中，当与单独的车辆或脾单个核细胞注射的小鼠相比。Th 1克隆的管理显着减少嗜酸性粒细胞的浸润，但增加了支气管周围的单核细胞。杯状细胞增生和支气管周围纤维化也受到抑制的Th 1克隆。Th 1细胞的转移显著降低气道反应性。Thl注射显著增加BALF中的干扰素γ，但显著降低白细胞介素（IL）-5和IL-13。Eotaxin mRNA主要在哮喘模型小鼠的肺中表达，而RANTES（调节活化，正常T细胞表达和分泌）在Thl transfer.In结论，结果表明，过继转移的T辅助细胞1型克隆可以抑制肺嗜酸性粒细胞和气道反应性，但增加非嗜酸性粒细胞炎症小鼠模型的哮喘。
T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma.Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5 %, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5 x 10(6.)body(-1)) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed.Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Thl injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Thl transfer.In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.