Target organ localization of memory CD4+ T cells in patients with chronic beryllium disease
Target organ localization of memory CD4+ T cells in patients with chronic beryllium disease
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DOI：
10.1172/jci200215846
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发表时间：
2002-11-01
影响因子：
15.9
通讯作者：
Kotzin, BL
中科院分区：
文献类型：
--
作者：
Fontenot, AP;Canavera, SJ;Kotzin, BL
慢性铍病（CBD）是由在工作场所接触铍引起的，它仍然是一个重要的公共卫生问题。有证据表明，CD4(+) T细胞在这种疾病的发展中起着关键作用。通过细胞内细胞因子染色，我们发现12例CBD患者肺（支气管肺泡灌洗液）中铍特异性CD4(+) T细胞的频率从1.4%到29%（平均17.8%）不等，这些T细胞对硫酸铍（BeSO4）反应表达th1型表型。很少，如果有的话，鉴定出铍特异性CD8(+) T细胞。相比之下，这些受试者血液中对铍有反应的CD4(+) T细胞的频率从检测不到到1 / 500不等。BeSO4暴露后，细胞内染色检测的支气管肺泡灌洗（BAL） CD4(+) T细胞频率与培养淋巴细胞增殖无相关性。表面标记物表达染色显示，几乎所有BAL T细胞都表现出效应记忆细胞表型。这些结果表明，在CBD患者的肺中，抗原特异性效应记忆CD4（+）细胞的频率和区隔化非常高。这些研究提供了深入了解抗原特异性T细胞入侵人类疾病中其他无法进入的靶器官的表型和功能特征。
Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace, and it remains an important public health concern. Evidence suggests that CD4(+) T cells play a critical role in the development of this disease. Using intracellular cytokine staining, we found that the frequency of beryllium-specific CD4(+) T cells in the lungs (bronchoalveolar lavage) of 12 CBD patients ranged from 1.4% to 29% (mean 17.8%), and these T cells expressed a Th1-type phenotype in response to beryllium sulfate (BeSO4). Few, if any, beryllium-specific CD8(+) T cells were identified. In contrast, the frequency of beryllium-responsive CD4(+) T cells in the blood of these subjects ranged from undetectable to 1 in 500. No correlation was observed between the frequency of beryllium-responsive bronchoalveolar lavage (BAL) CD4(+) T cells as detected by intracellular staining and lymphocyte proliferation in culture after BeSO4 exposure. Staining for surface marker expression showed that nearly all BAL T cells exhibit an effector memory cell phenotype. These results demonstrate a dramatically high frequency and compartmentalization of antigen-specific effector memory CD4(+) cells in the lungs of CBD patients. These studies provide insight into the phenotypic and functional characteristics of antigen-specific T cells invading other inaccessible target organs in human disease.