Saltini C, Winestock K, Kirby M, Pinkston P, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
N Engl J Med. 1989 Apr 27;320(17):1103-9. doi: 10.1056/NEJM198904273201702.
Chronic beryllium disease is characterized by the accumulation of helper/inducer T cells, macrophages, and granulomas in the lungs. To evaluate the hypothesis that the proliferation of CD4+ (helper/inducer) T cells in the lungs of patients with this disorder is maintained by local activation of beryllium-specific T-cell clones, we studied T cells obtained from peripheral blood and by bronchoalveolar lavage in eight patients and five healthy controls. The proliferation of T cells in response to beryllium in vitro was confined to the CD4+ T cells from the patients and was dependent on the presentation of antigen in the presence of both major histocompatibility complex class II antigens and functional interleukin-2 receptors. T cells from the patients' lungs had a significantly greater response to beryllium than did T cells from their peripheral blood (stimulation index, 103 vs. 5; P less than 0.01). Lines and clones of cells developed from T cells from the patients' lungs showed dose-dependent proliferation in response to beryllium but did not respond to recall antigens or to other metals. Although all beryllium-specific T-cell clones were CD4+ and none were CD8+ (suppressor/cytotoxic), all beryllium-specific clones studied had different rearrangements of T-cell antigen receptors, suggesting that the response to beryllium involved T cells with diverse specificities for beryllium. We conclude that in patients with chronic beryllium disease, beryllium acts as a class II-restricted antigen, stimulating local proliferation and accumulation in the lung of beryllium-specific CD4+ (helper/inducer) T cells. Hence, chronic beryllium disease is a hypersensitivity disease in which beryllium is the specific antigen.
慢性铍病的特征是肺内辅助/诱导性T细胞、巨噬细胞和肉芽肿的积聚。为了评估这种疾病患者肺内CD4 +（辅助/诱导）T细胞的增殖是由铍特异性T细胞克隆的局部激活所维持这一假说，我们研究了从8例患者和5名健康对照者的外周血及支气管肺泡灌洗中获取的T细胞。体外铍刺激下T细胞的增殖仅限于患者的CD4 + T细胞，并且依赖于主要组织相容性复合体II类抗原和功能性白细胞介素-2受体存在时抗原的呈递。患者肺内的T细胞对铍的反应明显大于其外周血T细胞（刺激指数分别为103和5；P<0.01）。从患者肺内T细胞培养出的细胞系和克隆显示对铍呈剂量依赖性增殖，但对回忆抗原或其他金属无反应。虽然所有铍特异性T细胞克隆均为CD4 +，无CD8 +（抑制/细胞毒性）克隆，但所研究的所有铍特异性克隆的T细胞抗原受体都有不同的重排，提示对铍的反应涉及对铍具有不同特异性的T细胞。我们得出结论，在慢性铍病患者中，铍作为II类限制性抗原，刺激铍特异性CD4 +（辅助/诱导）T细胞在肺内局部增殖和积聚。因此，慢性铍病是一种铍为特异性抗原的超敏反应性疾病。
