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

To investigate helper T (Th) cell subsets and cytokine production in patients with Vogt-Koyanagi-Harada's (VKH) disease.

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.

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.

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.