Analysis of intracellular cytokines in CD4(+) and CD8(+) lung and blood T cells in sarcoidosis

In pulmonary sarcoidosis, activated T cells accumulate in the lungs. We hyp othesized that the balance between the T-helper type 1 (Th1) cytokines (int erferon [IFN]-gamma and interleukin [IL]-2) and Th2 cytokines such as IL-4, IL-5, and IL-10 might explain differences in clinical outcome in pulmonary sarcoidosis, such as why patients of human leukocyte antigen (HLA) type DR 17 have a much better prognosis than those of other HLA types. Peripheral b lood lymphocytes (PBL) and lymphocytes obtained by bronchoalveolar lavage ( BAL) from HLA-typed sarcoidosis patients, as well as PBL from healthy contr ols, were stimulated in vitro, fixed, and permeabilized with saponin. There after, cells were stained with fluorescence-labeled antibodies specific for intracellular cytokines (IL-2, IL-4, IFN-gamma, and tumor necrosis factor (TNF)-alpha and cell surface markers CD4 and CD8, and were subjected to flo w-cytometric analysis. In bronchoalveolar lavage fluid (BALF), there were s ignificantly greater frequencies of T cells positive for IFN-gamma and TNF- alpha than there were among PBL, and significantly fewer cells positive for IL-4, in both the CD4(+) and CD8(+) subsets. HLA-DR17-positive patients sh owed a tendency toward a less pronounced Th1 response that may be related t o their good prognosis. Sarcoidosis patients had higher frequencies of cell s positive for IFN-gamma, IL-4, and IL-2 in their blood than did healthy co ntrols, a finding that may reflect the systemic nature of sarcoidosis. A cl ear Th 1 cytokine profile of CD4(+) as well as of CD8(+) T cells was demons trated in BALF from sarcoidosis patients. This was most pronounced for CD8( +) cells, which may therefore make an important contribution to the inflamm atory process in the lungs in pulmonary sarcoidosis.