Am. J. Respir. Cell Mol. Biol., Volume 18, Number 4, April, 1998 581-589

Expansions of T-cell Subsets Expressing Particular T-cell Receptor Variable Regions in Chronic Beryllium Disease

Andrew P. Fontenot, Brian L. Kotzin, Christine E. Comment, and Lee S. Newman

Departments of Medicine and Pediatrics, National Jewish Medical and Research Center; and Departments of Medicine, Preventive Medicine and Biometrics, and Immunology, University of Colorado Health Sciences Center, Denver, Colorado

Chronic beryllium disease (CBD) is a granulomatous disorder characterized by the presence of noncaseating granulomas and mononuclear cell inflammation, occurring in 1 to 5% of people exposed to beryllium in the workplace. In the lungs of affected patients, CD4⁺ T cells accumulate. Using anti-T-cell receptor (TCR) monoclonal antibodies, we investigated the TCR beta and alpha variable (V and V, respectively) repertoire in the bronchoalveolar lavage (BAL) and blood of both CBD patients and healthy controls. There was marked heterogeneity within the BAL CD4⁺ T-cell repertoire in both patients and controls. However, 11 of the 28 CBD patients demonstrated 16 different T-cell subset expansions within the BAL as compared with only one expansion in ten healthy controls. Five of the 16 expansions in CBD patients expressed V3. Altered TCR expression within the BAL T-cell repertoire appeared 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 in some individuals. These results provide additional insight into the involvement of CD4⁺ T cells in this disease and form the basis for studies to examine the nature of the stimulating antigen.

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