Interleukin-2 receptor gene expression by bronchoalveolar lavage lymphocytes in pulmonary sarcoidosis.
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.
Müller-Quernheim
J
J
Third Department of Internal Medicine, Johannes Gutenberg Universität, Mainz, Federal Republic of Germany.
Krönke
M
M
Strausz
J
J
Schykowski
M
M
Ferlinz
R
R
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008171:Lung Diseases / Q000235:genetics*; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D012507:Sarcoidosis / Q000235:genetics*; D013601:T-Lymphocytes / Q000032:analysis*
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2