Finotto Susetta, Neurath Markus F, Glickman Jonathan N, Qin Shixin, Lehr Hans A, Green Francis H Y, Ackerman Kate, Haley Kathleen, Galle Peter R, Szabo Susanne J, Drazen Jeffrey M, De Sanctis George T, Glimcher Laurie H
Critical Care and Pulmonary Division, Division of Gastroenterology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science. 2002 Jan 11;295(5553):336-8. doi: 10.1126/science.1065544.
Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.
人类哮喘与辅助性T细胞2（TH2）淋巴细胞浸润气道有关。我们观察到，与非哮喘患者气道中的T细胞相比，哮喘患者气道中的T细胞中TH1转录因子T-bet的表达降低，这表明T-bet的缺失可能与哮喘有关。T-bet基因靶向缺失的小鼠以及接受来自T-bet基因敲除小鼠的CD4+细胞的重症联合免疫缺陷小鼠，均自发表现出哮喘特有的多种生理和炎症特征。因此，在没有接触过敏原的情况下，T-bet缺乏会诱发一种类似于人类急慢性哮喘的小鼠表型。
