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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 characterized by granulomatous
inflammation and the accumulation of CD4+ T cells in the
lung. Patch testing of CBD patients with beryllium sulfate results in
granulomatous inflammation in the skin. We investigated whether the T
cell clonal populations present in the lung of CBD patients would also
be present in the involved skin of a positive beryllium patch test and
thus mirror the granulomatous process in the lung. CBD patients with
clonal TCR expansions in bronchoalveolar lavage (BAL) were selected for
study. All three CBD patients studied had a positive response to
beryllium sulfate application and a negative patch test to normal
saline. Immunohistochemistry showed extensive infiltration with
CD4+ T cells and few, if any, CD8+ T cells both
at 3 days and at later times when granulomas were apparent. T cell
infiltration early after skin testing appeared to be nonspecific with
the TCR repertoire of infiltrating T cells being distinct from that
present in BAL. At later times when granulomas were present, T cell
clones in skin overlapped with those in BAL in all patients tested.
Total TCR matches in skin and BAL were as high as 40% in selected V
T cell subsets. Studies of peripheral blood T cells before and after
patch testing provided evidence for mobilization of large numbers of
pathogenic beryllium-reactive T cells into the circulating pool. These
studies using skin patch testing provide new insight into the dynamics
of T cell influx and mobilization during granulomatous
inflammation.
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