CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation
CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hyperreactivity and inflammation
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DOI：
10.1067/mai.2002.127512
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发表时间：
2002-09-01
影响因子：
14.2
通讯作者：
Umetsu, DT
中科院分区：
文献类型：
--
作者：
Oh, JW;Seroogy, CM;Umetsu, DT
背景：T(H)2细胞在哮喘发病中起关键作用，但体内抑制T(H)2细胞功能的确切免疫机制尚不清楚。目的：我们研究的目的是确定产生IL-10的T细胞是否调节哮喘的发展。方法：我们使用基因疗法产生卵清蛋白特异性CD4 t辅助细胞来表达IL-10，我们检测了它们调节过敏原诱导的气道高反应性的能力。结果：我们证明了表达IL-10的CD4 T辅助细胞在卵清蛋白致敏和激发的BALB/c小鼠和用卵清蛋白特异性T(H)2效应细胞重组的SCID小鼠中消除了气道高反应性和气道嗜酸性粒细胞。分泌IL-10的t辅助细胞的抑制作用伴随着支气管肺泡灌洗液中IL-10数量的增加，具有抗原特异性，并通过中和IL-10而逆转。此外，在卵清蛋白致敏和攻毒的小鼠中，通过给药抗IL-10单抗来中和IL-10，严重加剧了气道的高反应性和气道炎症。结论：呼吸道黏膜分泌IL-10的T细胞确实可以调节T(H)2诱导的气道高反应性和炎症，强烈提示IL-10在变应性哮喘中具有重要的抑制作用。
Background: T(H)2 cells play a critical role in the pathogenesis of asthma, but the precise immunologic mechanisms that inhibit T(H)2 cell function in vivo are not well understood.Objective: The purpose of our studies was to determine whether T cells producing IL-10 regulate the development of asthma.Methods: We used gene therapy to generate ovalbumin-specific CD4 T-helper cells to express IL-10, and we examined their capacity to regulate allergen-induced airway hyperreactivity.Results: We demonstrated that the CD4 T-helper cells engineered to express IL-10 abolished airway hyperreactivity and airway eosinophilia in BALB/c mice sensitized and challenged with ovalbumin and in SCID mice reconstituted with ovalbumin-specific T(H)2 effector cells. The inhibitory effect of the IL-10-secreting T-helper cells was accompanied by the presence of increased quantities of IL-10 in the bronchoalveolar lavage fluid, was antigen-specific, and was reversed by neutralization of IL-10. Moreover, neutralization of IL-10 by administration of anti-IL-10 mAb in mice sensitized and challenged with ovalbumin seriously exacerbated airway hyperreactivity and airway inflammation.Conclusion: Our results demonstrate that T cells, secreting IL-10 in the respiratory mucosa can indeed regulate T(H)2-induced airway hyperreactivity and inflammation, and they strongly suggest that IL-10 plays an important inhibitory role in allergic asthma.