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

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.

Patients receiving murine monoclonal antibody therapy for malignancy develop T cells that proliferate in vitro in response to these antibodies as antigens

“…This antibody has specificity for the low affinity subunit of the receptor for IL-2, but it is recognised that both low and high affinity IL-2 receptor subunits are needed for T cell activation by IL-2 (Robb et al, 1984). This finding in association with the increased percentage of CD4 + lymphocytes as well as the CD4/CD8 ratio after MAb stimulation is consistent with the activation of the T helper/inducer population and the generation of a delayed type-like hypersensitivity response (Saltini et al, 1989). Another pathway of antigen specific T cell activation is the CD2 surface antigen, which binds the LFA-3 molecule on the antigen presenting cell, and this is essential to allow any specific recognition of the antigen-MHC complex by the T cell receptor (Hunig et al, 1987).…”

An industrial risk: Beryllium

“…37 KBH'da ise BAL'daki mevcut makrofaj ve lenfositlerin sayı ve oranında belirgin bir yükseliş görülür. 9,38 Bu lenfositlerin çoğu CD4+ T hücreleri-dir 38-40 ve KBH'nın patogenezinde önemli rol oynarlar. 24,37,41,42 KBH'lı bireylerin akciğerlerinde CD4+ T hücreleri aktive olduğunda, bu hücreler klonal olarak proliferasyon göstermekte ve IL-2, IFN-γ ve tü-mör nekroz faktörü (TNF-α) gibi Th-1 tipi sitokinleri salgılamaktadır.…”

“…9 BeLPT, çözünebi-lir berilyum tuzları varlığında periferal kandan alınan lenfositlerdeki proliferasyonu tespit eder. KBH ise BeS'ten farklı olarak akciğer dokusunda non-kazeöz granuloma ve mononükleer hücre infiltrasyonunun varlığı ile ayırt edilebilir.…”

Beryllium-Induced TNF-α Production Is Transcription-Dependent in Chronic Beryllium Disease

“…BAL cells (5 ϫ 10 5 cells) were placed in polypropylene tubes (12 ϫ 75 mm; Fisher Scientific Co., Denver, CO) containing 1 ml of complete culture media plus either medium alone, 10 ng/ml SEB, or 10 M BeSO 4 . SEB was used as a positive control for the activation of BAL CD4 ϩ T cells for TNF-␣ production as previously demonstrated (2,7,20).…”