哮喘联盟

    背景：T(H)1-特定转录因子，T型中蛋白表达的T细胞 （T-bet)，通过不同机制控制TH细胞分泌TH1和TH2型细胞因子。T-bet缺陷小鼠产生过量的TH2细胞因子并出现自发性气道炎症。
    目的：测试T-bet过度表达是否可抑制哮喘发生。
    方法：我们制备了一种T细胞特异性、具备T-bet缺陷遗传背景但可诱导产生T-bet的转基因小鼠，并用它来研究在卵蛋白(OVA)诱发哮喘模型中T-bet的功能。
    结果：通过T细胞特异模式诱导产生的T-bet 可抑制哮喘模型小鼠产生气道高反应，嗜酸性粒细胞和淋巴细胞性炎症，抑制支气管肺泡灌洗液中产生IL-5和IL-13，降低血清IgE抗体滴度和外周血T细胞产生的TH2类细胞因子。哮喘炎症后期诱导表达的T-bet仍可抑制气道高反应性、杯状细胞增生、和TH2细胞因子的产生。
    结论：实验结果表明T细胞表达的T-bet可以防止气道炎症的发生和发展，这一结论可能延伸至人类哮喘。

（陈欣 审校）
Park JW, et al. J Allergy Clin Immunol. 2008 Dec 9. [Epub ahead of print]

Restoration of T-box-containing protein expressed in T cells expression in T cells protects against allergen-induced asthma.

Park JW, Min HJ, Sohn JH, Kim JY, Hong JH, Sigrist KS, Glimcher LH, Hwang ES.
Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.

BACKGROUND: A T(H)1-specific transcription factor, T-box-containing protein expressed in T cells (T-bet), controls the production of both T(H)1 and T(H)2 cytokines in T(H) cell differentiation by means of distinct mechanisms. T-bet-deficient mice overproduce T(H)2 cytokines and have spontaneous airway inflammation.
OBJECTIVES: We tested whether T-bet overexpression could protect against the development or progression of asthma.
METHODS: We generated a T cell-specific and inducible line of T-bet-transgenic mice on a T-bet-deficient genetic background and used it to study the function of T-bet in an ovalbumin (OVA)-induced asthma model.
RESULTS: Induction of T-bet in a T cell-specific manner in an OVA model of asthma concomitant with OVA injection prevented airway hyperresponsiveness, eosinophilic and lymphocytic inflammation, and IL-5 and IL-13 production in bronchoalveolar lavage fluid and also reduced serum IgE and T(H)2 cytokine production by peripheral T cells. Even when T-bet expression was induced during later stages of asthma progression, T-bet overexpression still attenuated airway hyperresponsiveness and goblet cell hyperplasia, as well as T(H)2 cytokine production.
CONCLUSIONS: Our results suggest that T-bet expression in T cells can prevent the initiation of airway inflammation and progression of chronic inflammation and might be extrapolated to human asthma.