Highly activated T-cell receptor AV2S3(+) CD4(+) lung T-cell expansions inpulmonary sarcoidosis

Sarcoidosis is a systemic disorder of unknown origin, primarily affecting t he lungs. The granulomatous inflammation is driven by the interplay between various molecules and cells, including T cells. Previously, our group repo rted a close correlation between lung-restricted T-cell receptor (TCR) AV2S 3 CD4-positive T-cell expansions and HLA-DR17 in active sarcoidosis. The ai m of this study was to characterize phenotypically such AV2S3 lung T cells, to obtain more information about the state of activation of this intriguin g T-cell subset. Bronchoalveolar lavage (BAL) was performed on sarcoidosis patients with active disease and on healthy control subjects (HC). The expr ession of activation and subset markers was evaluated and compared between BAL AV2S3-positive and AV2S3-negative T cells of patients with lung-restric ted AV2S3 T-cell expansions, and between BAL and peripheral blood lymphocyt es (PBL) of patients, and HC. The frequency of cells expressing activation markers CD26, CD28 CD69, and HLA-DR was enhanced in AV2S3-positive versus A V2S3-negative BAL CD4(+) T-cell subsets. In contrast, CD25 (II-2R) and CD27 were expressed at lower levels by the AV2S3-positive CD4(+) lung T cells. Our data confirm a substantial activation of BAL CD4(+) T cells of patients with sarcoidosis. Furthermore, the AV2S3 CD4-positive lung cells display a pattern of activation markers, suggesting that they are significantly more activated compared with lung CD4(+) T cells expressing other TCR V gene se gments as well as compared with BAL CD4(+) T cells of HC. These results sup port our hypothesis of an ongoing and selective stimulation of AV2S3 T cell s by a specific antigen and the participation of this subset in the inflamm atory process in the lungs of patients with sarcoidosis.