Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells.
Publication Type | Academic Article |
Authors | Saltini C, Winestock K, Kirby M, Pinkston P, Crystal R |
Journal | N Engl J Med |
Volume | 320 |
Issue | 17 |
Pagination | 1103-9 |
Date Published | 04/27/1989 |
ISSN | 0028-4793 |
Keywords | Alveolitis, Extrinsic Allergic, Berylliosis, Beryllium, T-Lymphocytes, Helper-Inducer |
Abstract | 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. |
DOI | 10.1056/NEJM198904273201702 |
PubMed ID | 2469014 |