Maintenance of Alveolitis in Patients with Chronic Beryllium Disease by Beryllium-Specific Helper T Cells

Cesare Saltini, Karen Winestock, Martha Kirby, Paula Pinkston, Ronald Crystal

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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<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. THE inhalation of beryllium dusts, salts, or fumes is associated with two types of pulmonary disease: an acute chemical pneumonitis caused by short exposures to high concentrations, and a chronic interstitial granulomatous lung disorder caused by lower levels of exposure over months to years.1 2 3 4 The acute pneumonitis is probably caused by direct injury of the lung by beryllium, whereas the chronic pulmonary disease is associated with an alveolitis characterized by a diffuse accumulation of lymphocytes and mononuclear phagocytes in the alveolar structures and the formation of noncaseating granulomas — features suggestive of a chronic, delayed-type hypersensitivity reaction.5 6 7 8 9 The concept that…

Original languageEnglish
Pages (from-to)1103-1109
Number of pages7
JournalNew England Journal of Medicine
Volume320
Issue number17
DOIs
Publication statusPublished - 27 Apr 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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