EXPANSIONS OF T-CELL SUBSETS EXPRESSING PARTICULAR T-CELL RECEPTOR VARIABLE REGIONS IN CHRONIC BERYLLIUM DISEASE

Chronic beryllium disease (CBD) is a granulomatous disorder characteri zed by the presence of noncaseating granulomas and mononuclear cell in flammation, occurring in 1 to 5% of people exposed to beryllium in the workplace. In the lungs of affected patients, CD4(+) T cells accumula te. Using anti-T-cell receptor (TCR) monoclonal antibodies, we investi gated the TCR beta and alpha variable (V beta and V alpha, respectivel y) repertoire in the bronchoalveolar lavage (BAL) and blood of both CB D patients and healthy controls. There was marked heterogeneity within the BAL CD4(+) T-cell repertoire in both patients and controls. Howev er, 11 of the 28 CBD patients demonstrated 16 different T-cell subset expansions within the BAL as compared with only one expansion in ten h ealthy controls. Five of the 16 expansions in CBD patients ex pressed V beta 3. Altered TCR expression within the BAL T-cell repertoire appe ared to persist over time in patients who underwent repeat evaluation. After in vitro stimulation of BAL T cells with beryllium sulfate and interleukin-2, we noted further alteration of the BAL TCR repertoire i n some individuals. These results provide additional insight into the involvement of CD4(+) T cells in this disease and form the basis for s tudies to examine the nature of the stimulating antigen.