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 hypothesized that the balance between the T-helper type 1 (Th1) cytokines (interferon [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 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 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 flow-cytometric analysis. In bronchoalveolar lavage fluid (BALF), there were significantly 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 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 IFN-gamma, 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+ as well as of CD8+ T cells was demonstrated in BALF from sarcoidosis patients. This was most pronounced for CD8+ cells, which may therefore make an important contribution to the inflammatory process in the lungs in pulmonary sarcoidosis.
Wahlström
J
J
Microbiology and Tumour Biology Centre, Karolinska Institutet, and Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Katchar
K
K
Wigzell
H
H
Olerup
O
O
Eklund
A
A
Grunewald
J
J
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry*; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000737:chemistry; D008168:Lung / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000097:blood / Q000276:immunology*
D016207:Cytokines