CD4+ invariant T-cell-receptor plus natural killer T cells in bronchial asthma.
CD4+ invariant T-cell-receptor plus natural killer T cells in bronchial asthma.
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DOI：
10.1056/nejmoa053614
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发表时间：
2006-03-16
影响因子：
158.5
通讯作者：
Umetsu, DT
中科院分区：
文献类型：
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作者：
Akbari, O;Faul, JL;Umetsu, DT
背景：支气管哮喘与炎症过程相关，其特征是气道中存在大量产生白细胞介素 4 和白细胞介素 13 的 CD4+ T 细胞。然而，CD4 抗原不仅由 II 类主要组织相容性复合体 (MHC) 限制性 CD4+ T 细胞表达，而且还由新鉴定的 T 细胞亚群、CD1d 限制性自然杀伤 T 细胞表达。这些细胞表达保守（不变）T 细胞受体并具有有效的免疫调节功能。由于过敏性哮喘小鼠模型表明自然杀伤 T 细胞是过敏原诱导的气道高反应性发生所必需的，因此我们假设自然杀伤 T 细胞在人类哮喘中发挥重要作用。 方法：我们使用 CD1d-四聚体、自然杀伤 T 细胞特异性抗体，以及恒定 T 细胞受体的逆转录酶聚合酶链反应分析 研究人员对自然杀伤 T 细胞进行了检测，以评估 14 名哮喘患者的肺部和循环血液中自然杀伤 T 细胞的频率和分布。结果：中重度持续性哮喘患者中约 60% 的肺部 CD4+CD3+ 细胞不是 II 类 MHC 限制性 CD4+ T 细胞，而是自然杀伤 T 细胞。自然杀伤 T 细胞表达不变的 T 细胞受体并产生 2 型辅助细胞因子。相比之下，在结节病患者肺部发现的 CD4+ T 细胞是传统的 CD4+ CD3+ T 细胞，而不是自然杀伤 T 细胞。结论：与小鼠研究表明，过敏原诱导的气道高反应性的发展需要自然杀伤 T 细胞，我们的结果强烈表明 CD4+ 自然杀伤 T 细胞在人类哮喘中发挥着重要的致病作用。
Background: Bronchial asthma is associated with an inflammatory process that is characterized by the presence in the airways of large numbers of CD4+ T cells producing interleukin-4 and interleukin-13. However, the CD4 antigen is expressed not only by class II major histocompatibility complex (MHC)-restricted CD4+ T cells, but also by a newly identified subgroup of T cells, CD1d-restricted natural killer T cells. These cells express a conserved (invariant) T-cell receptor and have a potent immunoregulatory function. Because mouse models of allergic asthma indicate that natural killer T cells are required for the development of allergen-induced airway hyperreactivity, we hypothesized that natural killer T cells play an important role in human asthma.Methods: We used CD1d-tetramers, antibodies specific for natural killer T cells, as well as reverse-transcriptase-polymerase-chain-reaction analysis of the invariant T-cell receptor of natural killer T cells to assess the frequency and distribution of natural killer T cells in the lungs and in the circulating blood of 14 patients with asthma.Results: About 60 percent of the pulmonary CD4+CD3+ cells in patients with moderate-to-severe persistent asthma were not class II MHC-restricted CD4+ T cells but, rather, natural killer T cells. The natural killer T cells expressed an invariant T-cell receptor and produced type 2 helper cytokines. In contrast, the CD4+ T cells found in the lungs of patients with sarcoidosis were conventional CD4+CD3+ T cells, not natural killer T cells.Conclusions: Together with studies in mice indicating a requirement for natural killer T cells in the development of allergen-induced airway hyperreactivity, our results strongly suggest that CD4+ natural killer T cells play a prominent pathogenic role in human asthma.