Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in patients with beryllium-induced disease

J Allergy Clin Immunol. 2005 May;115(5):1036-42. doi: 10.1016/j.jaci.2005.01.019.


Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Allergens / adverse effects*
  • Beryllium / adverse effects*
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Disease Progression
  • Female
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / immunology*
  • Immunization*
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Species Specificity


  • Allergens
  • Interleukin-2
  • Interferon-gamma
  • Beryllium