Cytokine production and helper T cell subsets in Vogt-Koyanagi-Harada’s disease

Abstract

PURPOSE: To investigate helper T (Th) cell subsets and cytokine production in patients with Vogt-Koyanagi-Harada's (VKH) disease. METHODS: Nine patients in the acute stage of VKH disease and 9 healthy controls were studied. Interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and IL-4 mRNA from peripheral blood mononuclear cells (PBMC) was detected by reverse transcriptase-polymerase chain reaction. Cytokine levels in plasma, cerebrospinal fluid (CSF) and PBMC culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The proportions of each cytokine-producing CD4+ or CD8+ cells in PBMC cultured with or without anti-CD3 antibody stimulation were analyzed by flow cytometry. RESULTS: We observed a significant increase of cytokine mRNA positive cases of VKH patients in comparison with controls only in IFN-gamma mRNA detection from PBMC. ELISA detected IFN-gamma in CSF from only 1 patient and no cytokine in plasma. The levels of IFN-gamma and IL-2 were significantly higher in the stimulated cell culture supernatant of the patients than those of controls. The proportions of IFN-gamma- or IL-2-producing CD4+ cells were significantly higher in the patients than in controls in both stimulated and unstimulated conditions. However, no significant difference was found in IL-4-producing CD4+ cells. In CD8+ cells, significant difference was found only in IL-2-producing cells in the stimulated condition. CONCLUSIONS: Th cells from VKH patients produced predominantly Th1 cytokines, especially after stimulation in vitro. It is therefore suggested that activated Th cells produce predominantly Th1 cytokines, which then produce pathologic changes.