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 numbers, and a subset of these cells is activated. By using both quantitative PCR and anti- Vβ mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR Vβ expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few Vβ-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, demonstrated a selective expansion of particular Vβ- expressing subsets. Interestingly, different Vβ-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results 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 insight into the pathogenesis of this disease.