Interleukin-2 Receptor Gene Expression by Bronchoalveolar Lavage Lymphocytes in Pulmonary Sarcoidosis

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Abstract
Current concepts of the immunopathogenesis of sarcoidosis favor a central role of activated, interleukin-2 (IL-2) producing helper T-cells at sites of inflammation. Normally, activated T-cells release IL-2 and express IL-2 receptors (IL-2R). IL-2R+ cells, however, are not uniformly found in patients with clinically active disease. To determine whether the lack of IL-2R+ cells is caused by a dysregulation of the IL-2R gene or by the mode of T-cell activation in pulmonary sarcoidosis, we quantified IL-2 and IL-2R m-RNA transcripts, IL-2 release, and IL-2R surface protein in peripheral blood lymphocytes of patients with sarcoidosis and normal control subjects before and after in vitro stimulation as a function of time. Additionally, we determined the percentage of IL-2R+ bronchoalveolar lavage (BAL) and peripheral blood lymphocytes in our study population and evaluated the in vivo transcriptional activity of the IL-2R gene. In peripheral blood lymphocytes, maximal IL-2R mRNA accumulation is found between 6 and 24 h, and maximal accumulation of IL-2 mRNA is found between 24 and 48 h. No differences emerged between normal subjects and patients with sarcoidosis. In six of 19 patients, we observed elevated numbers of IL-2R+ BAL lymphocytes and found IL-2R mRNA in those cells. These results are in accordance with the concept of a compartmentalized T-cell activation in sarcoidosis, resulting in IL-2 and IL-2R positive BAL cells and quiescent peripheral blood lymphocytes.