Down-regulation of IFN-γ-producing CD56+ T cells after combined low-dose cyclosporine/prednisone treatment in patients with Behcet's uveitis

PURPOSE. To investigate the effects of combined low-dose cyclosporine and prednisone (Cs/Pd) treatment on circulating CD56(+) T cells in patients with Behcet's uveitis. METHODS. Ten patients with Behc, et's uveitis and 10 healthy control subjects were prospectively recruited. The patients were treated with Cs/Pd for 2 months. Phenotypic and functional changes in circulating CD56(+) T cells were assayed before and after treatment. CD56(+) T-cell subsets were determined by flow cytometric analysis with monoclonal antibodies for CD3, CD4, CD8, CD56, pan gamma delta TCR, and V alpha 24. The absolute numbers of cells in the lymphocyte subsets were calculated. Cytokine (IFN-gamma, IL-4, and IL-10) expressions were measured by ELISA and by intracellular cytokine staining. RESULTS. The proportions of CD56(+) T cells, specifically CD8(high)CD56(+) and CD56(+)gamma delta T-cell subsets, were significantly higher in active Behc, et's uveitis but normalized after treatment, whereas the total T-lymphocyte count and the absolute numbers of CD56(+) T cells were unaffected by treatment. The levels of IFN-gamma and IL-4 were elevated in aqueous humor and serum in Behc, et's uveitis (P < 0.001), whereas IL-10 was not detected. After treatment, serum IL-4 levels markedly increased (P < 0.001), and IFN-gamma production by circulating CD56(+) T cells was then suppressed. IL-4 and -10 production by CD56(+) T cells was increased by treatment, but in contrast, minimal changes were found in CD56(+) T cells. CONCLUSIONS. The results imply that Cs/Pd treatment for Behc, et's uveitis selectively affects the population of and the cytokine expression in CD56(+) T cells, but without significant changes in CD56(+) T cells, and that IFN-gamma-producing CD56(+) T cells are the central pathogenic immune cells in Behc, et's uveitis.