TCR EXPRESSION OF ACTIVATED T-CELL CLONES IN THE LUNGS OF PATIENTS WITH PULMONARY SARCOIDOSIS

Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4(+) T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4(+) T cells accumulate in large nu mbers, and a subset of these cells is activated. By using both quantit ative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of tota l and activated bronchoalveolar lavage T cells, the latter subset bein g defined by the ability to proliferate in short-term culture suppleme nted with IL-2. Overall, there was little difference when TCR V beta e xpression of freshly isolated lung and peripheral blood cells was comp ared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demon strated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in diff erent patients. Junctional region sequencing indicated that the prolif erating T cells in culture were strikingly oligoclonal and were derive d from T cell clones already selectively expanded in vivo. These resul ts provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4(+) T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide i nsight into the pathogenesis of this disease.