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,§,¶
,§,§,¶
Departments of
*
Medicine,
Immunology, and
Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, CO 80262; and Departments of
§
Medicine and
¶
Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206
Chronic beryllium disease (CBD) is caused by beryllium exposure and
is characterized by granulomatous inflammation with accumulation of
CD4+ T cells in the lung. We analyzed TCR ß-chain and
-chain genes expressed by these CD4+ T cells. In the
lungs of individual patients, as well as among four of five CBD
patients studied, different oligoclonal expansions within the Vß3
subset were found to express homologous or even identical CDR3 amino
acid sequences. These related expansions were specific for CBD
patients, were compartmentalized to lung, and persisted at high
frequency in patients with active disease. Limiting dilution cloning
and analysis of coexpressed TCR -chain genes confirmed that these
TCRs were selectively expanded by a common Ag involving beryllium.
Overall, homologous TCR ß- and -chains showed identical V regions
and invariant charged residues within the CDR3 but considerable
variability in TCRJ usage. Remarkably, CBD patients expressing nearly
identical TCRs did not share common HLA-DRB1 or DQ alleles. These
results implicate particular CD4+ cells in the pathogenesis
of CBD and provide insight into how beryllium is recognized in human
disease.
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