Lung and Blood T Cells in Sarcoidosis

In pulmonary sarcoidosis, activated T cells accumulate in the lungs. We hypothesized that the balance between the T-helper type 1 (Th1) cytokines (interferon [IFN]g 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 DR17 have a much better prognosis than those of other HLA types. Peripheral blood lymphocytes (PBL) and lymphocytes obtained by bronchoalveolar lavage (BAL) from HLA-typed sarcoidosis patients, as well as PBL from healthy controls, were stimulated in vitro , fixed, and permeabilized with saponin. Thereafter, cells were stained with fluorescencelabeled antibodies specific for intracellular cytokines (IL-2, IL-4, IFNg , and tumor necrosis factor (TNF)a and cell surface markers CD4 and CD8, and were subjected to flow-cytometric analysis. In bronchoalveolar lavage fluid (BALF), there were significantly greater frequencies of T cells positive for IFNg and TNFa than there were among PBL, and significantly fewer cells positive for IL-4, in both the CD4 1 and CD8 1 subsets. HLA-DR17–positive patients showed a tendency toward a less pronounced Th1 response that may be related to their good prognosis. Sarcoidosis patients had higher frequencies of cells positive for IFNg , IL-4, and IL-2 in their blood than did healthy controls, a finding that may reflect the systemic nature of sarcoidosis. A clear Th1 cytokine profile of CD4 1 as well as of CD8 1 T cells was demonstrated in BALF from sarcoidosis patients. This was most pronounced for CD8 1 cells, which may therefore make an important contribution to the inflammatory process in the lungs in pulmonary sarcoidosis.