Frequency of beryllium-specific, T H1-type cytokine-expressing CD4 + T cells in patients with beryllium-induced disease

Abstract

Beryllium sensitization is caused by exposure to beryllium in the workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and granulomatous inflammation. Whether biomarkers are present in blood that would allow separation of CBD from beryllium sensitization without invasive pulmonary procedures is unknown. The aim of this study was to determine whether the quantity of beryllium-specific T cells in blood of patients with CBD differs from that found in BeS subjects. Beryllium-induced T-cell proliferation and T H 1-type cytokine secretion were determined in blood cells from 33 patients with CBD and 18 BeS subjects. We demonstrate here that patients with CBD have a significantly elevated number of IFN-gamma-producing and IL-2-producing beryllium-specific CD4+ T cells in blood compared with both BeS and normal control subjects. In contrast, no difference in beryllium-induced proliferation of blood T cells was seen between BeS patients and patients with CBD. Compared with the blood beryllium lymphocyte proliferation test, which detected beryllium-induced proliferation in 65% of BeS patients and patients with CBD, ELISPOT analysis detected IFN-gamma secretion in 80% of these subjects. Higher numbers of beryllium-specific cells in blood were also associated with the extent of alveolar inflammation, as measured by both bronchoalveolar lavage white blood cell and lymphocyte counts. The frequency of beryllium-specific T cells in the blood of beryllium-exposed subjects may be a useful biomarker that helps discriminate between beryllium sensitization and progression to CBD.