Beryllium-specific CD4 + T cells in blood as a biomarker of disease progression

Abstract

CD4(+) T cells are responsible for the progressive lung damage seen in patients with chronic beryllium disease (CBD), a granulomatous lung disorder in which antigen-specific, T(H)1-type, cytokine-secreting T cells have been characterized. Compared with those seen in beryllium (Be)-sensitized subjects, increased numbers of Be-responsive T cells are present in the blood of patients with CBD. The aim of this study was to determine whether the number of Be-specific T cells in blood predicted the development of CBD in a cohort of Be-exposed subjects. Using IFN-γ ELISpot and proliferation-based assays, we determined the frequency and proliferative capacity of Be-responsive T cells in blood. Compared with the Be lymphocyte proliferation test, which detected an abnormal Be-induced proliferative response in 11 (4.2%) of 260 workers from a Be-machining facility, the IFN-γ ELISpot detected a sensitization rate of 10% (χ(2) = 55.7, P < .0001). A significant positive correlation was also noted between the number of Be-responsive CD4(+) T cells in the blood and lung tissue of patients with CBD. Importantly, the transition from Be sensitization to CBD was associated with an increased number of antigen-specific T cells in blood. These findings have important implications for Be-induced disease and potentially other immune-mediated disorders, suggesting that the frequency of antigen-specific T cells in blood can serve as a noninvasive biomarker to predict disease development and severity of the Be-specific CD4(+) T-cell alveolitis.