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

Abstract

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 Behcet'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 gammadelta TCR, and Valpha24. 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 CD8highCD56+ and CD56+gammadelta T-cell subsets, were significantly higher in active Behcet'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 Behcet'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 Behcet'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 Behcet's uveitis.