哮喘CD4+恒定T细胞受体+自然杀伤T细胞
2007/03/09
哮喘患者气道内存在大量CD4+T淋巴细胞，CD4+的表达不仅存在于II型组织抗原相容复合物限制的CD4+T淋巴细胞，而且存在于T淋巴细胞的一个亚群-CD1d限制的自然杀伤T细胞。本研究观察了这一亚群T淋巴细胞在哮喘患者中的作用。
作者选择了14例哮喘患者，5例结节病患者和6例健康对照。观察了不同人群的血清IgE水平及肺功能；比较了不同人群支气管肺泡盥洗液中细胞分类，哮喘患者CD4+恒定自然杀伤T细胞明显增多；流式细胞计数显示， 在哮喘组，支气管肺泡盥洗液中CD4+细胞多为恒定T细胞受体+的自然杀伤T细胞，相同的结果通过免疫荧光染色和反转录PCR得到证实；从哮喘患者支气管肺泡盥洗液中纯化的CD4+恒定T细胞受体+的自然杀伤T细胞可分泌较多的IL-4和IL-13，但较少的γ干扰素，而哮喘和结节病患者外周血上述细胞群三种细胞因子均有分泌。
作者因此认为CD4+的自然杀伤细胞在哮喘发病中有重要作用。
作者选择了14例哮喘患者，5例结节病患者和6例健康对照。观察了不同人群的血清IgE水平及肺功能；比较了不同人群支气管肺泡盥洗液中细胞分类，哮喘患者CD4+恒定自然杀伤T细胞明显增多；流式细胞计数显示， 在哮喘组，支气管肺泡盥洗液中CD4+细胞多为恒定T细胞受体+的自然杀伤T细胞，相同的结果通过免疫荧光染色和反转录PCR得到证实；从哮喘患者支气管肺泡盥洗液中纯化的CD4+恒定T细胞受体+的自然杀伤T细胞可分泌较多的IL-4和IL-13，但较少的γ干扰素，而哮喘和结节病患者外周血上述细胞群三种细胞因子均有分泌。
作者因此认为CD4+的自然杀伤细胞在哮喘发病中有重要作用。
（刘颖格 西安，第四军医大学西京医院呼吸内科 710032 摘译）
(N Engl J Med ，2006，354:1117-1129)
CD4+ Invariant T-Cell–Receptor+ Natural Killer
T Cells in Bronchial Asthma
Omid Akbari, Ph.D., John L. Faul, M.D., Elisabeth G. Hoyte, M.S.N., Gerald J. Berry, M.D., Jan Wahlstrom, M.D., Ph.D.,
Mitchell Kronenberg, Ph.D., Rosemarie H. DeKruyff, Ph.D., and Dale T. Umetsu, M.D., Ph.D.
Mitchell Kronenberg, Ph.D., Rosemarie H. DeKruyff, Ph.D., and Dale T. Umetsu, M.D., Ph.D.
ABSTRACT
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.
N Engl J Med,2006,355:1682-1689
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