TH1/TH2 and TC1/TC2 profiles in peripheral blood and bronchoalveolar lavage fluid cells in pulmonary sarcoidosis.
BACKGROUND
Sarcoidosis is thought to be a type-1 cytokine-mediated disorder. However, few data are available on the profiles of cytokine expression by TH cells at the single-cell level, as assessed by intracellular cytokine flow cytometry. Additionally, it remains to be determined whether the balance of TC1 and TC2 cells can be altered in sarcoidosis.


OBJECTIVE
The aim of this study was to evaluate the TH1/TH2 and TC1/TC2 balances in sarcoidosis.


METHODS
Using triple-color flow cytometry and phorbol 12-myristate acetate/ionomycin stimulation, we measured the production of the intracellular cytokines IFN-gamma and IL-4 in CD4+ and CD8+ T cells separately, which were obtained from peripheral blood and bronchoalveolar lavage fluid (BALF) of 20 patients with sarcoidosis, and compared their cytokine expressions with those of 10 normal subjects.


RESULTS
Under unstimulated conditions, there were no significant differences in the proportion of cytokine-producing CD4+ or CD8+ T cells in peripheral blood or BALF between patients with sarcoidosis and normal control subjects. On stimulation with phorbol 12-myristate acetate/ionomycin for 4 hours, in BALF of the patients, but not in peripheral blood, we found a significant increase in the percentage of IFN-gamma-producing CD4+ T cells and a decrease in the percentage of IL-4-producing CD4+ T cells, resulting in a 3.5-fold higher ratio of IFN-gamma/IL-4-producing CD4+ T cells compared with that found in normal subjects. In contrast, no difference was found in the proportions of cytokine-producing CD8+ T cells or the ratio of IFN-gamma/IL-4-producing CD8+ T cells in either the peripheral blood or BALF between the patients and normal subjects.


CONCLUSIONS
These findings suggest that the prominent shift toward a type-1 phenotype may occur in CD4+ T-cell populations but not in CD8+ T-cell populations in the affected organs of sarcoidosis.
Inui
N
N
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
Chida
K
K
Suda
T
T
Nakamura
H
H
D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000145:classification* / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D008171:Lung Diseases / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012507:Sarcoidosis / Q000097:blood* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells; D018418:Th2 Cells
D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate