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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 (Vbeta and Valpha, 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 Vbeta3. 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.

In utero exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was found to alter expression of murine thymocyte fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 1.5, or 3.0 micrograms TCDD/kg/day in corn oil on gestational days (gd) 6-14. Offspring were examined on gd 18 and postnatally on d6, d14, and d21, and at 7, 8, and 10 weeks of age. Severe thymic atrophy and cellular depletion were found both pre- and postnatally in TCDD-exposed mice. Immunocytochemical localization of the Thy 1.2 antigen on gd 18 thymocytes revealed no TCDD-related changes in cellular distribution. Flow cytometric analysis, however, indicated that the TCDD treatment resulted in a significant decrease in the percentage of CD4+8+ fetal thymocytes, as well as significantly increased CD4-8- and CD4-8+ thymocytes. The increased CD4-8+ population after TCDD was not from induction of Ts cells. At 7-8 weeks postnatally, no differences existed between control and treatment groups in mitogen responses and antibody plaque response. However, altered thymocyte antigen expression was found to correlate with altered postnatal immune function, as evidenced by decreased cytotoxic T lymphocyte response at 8 weeks of age. Taken together, these results indicate that immunosuppression following prenatal exposure to TCDD can be readily detected by qualitative and quantitative changes in the cell surface phenotype of fetal thymocytes. Furthermore, the observed altered distribution suggests that TCDD inhibits normal thymocyte maturational processes.

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