TH1/TH2 and TC1/TC2 profiles in peripheral blood and bronchoalveolar lavage fluid cells in pulmonary sarcoidosis

Abstract

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-γ 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-γ–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-γ/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-γ/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. (J Allergy Clin Immunol 2001;107:337-44.)