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Diminished Frequency and Function of CD4⁺CD25^high Regulatory T Cells Associated with Active Uveitis in Vogt-Koyanagi-Harada Syndrome

¹From the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center of Sun Yat-sen University and ²International Uveitis Study Laboratory of Guangdong Province, Guangzhou, People’s Republic of China; the ³Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht, The Netherlands; and the ⁴Animal Sciences Group, Wageningen UR, Lelystad, The Netherlands.

PURPOSE. CD4⁺CD25^high regulatory T (Treg) cells have been shown to be involved in the pathogenesis of autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is an organ-specific autoimmune disease. This study was designed to phenotypically and functionally characterize peripheral blood CD4⁺CD25^high Treg cells in VKH patients with active uveitis.

METHODS. Blood samples were taken from 30 patients with active VKH, 19 patients with inactive VKH, and 26 healthy controls. Peripheral blood mononuclear cells were subjected to flow cytometry for analysis of phenotypes of the CD4⁺CD25^high Treg cells. For functional analysis, CD4⁺CD25^high Treg cells and CD4⁺CD25^– T cells were separated by means of magnetic-assisted cell sorting and subsequently cocultured for 6 days. The proliferation of CD4⁺CD25^– T cells was measured by [³H] thymidine incorporation assay. The levels of IFN-, IL-17, and IL-13 in the supernatants were determined by enzyme-linked immunosorbent assay.

RESULTS. Significantly decreased frequencies of CD4⁺CD25^high Treg cells and percentages of FOXP3⁺ cells in these Treg cells were shown in patients with active VKH. Treg cells from patients with active VKH showed a significant deficiency in suppressing the proliferation of CD4⁺CD25^– T cells and inhibiting the production of IFN- and IL-13 by CD4⁺CD25^– T cells. CD4⁺CD25^high Treg cells from VKH patients or healthy controls did not markedly inhibit or promote IL-17 production.

CONCLUSIONS. A significantly decreased frequency and diminished function of CD4⁺CD25^high Treg cells is associated with active uveitis in patients with VKH syndrome. These results suggest that these dysfunctional CD4⁺CD25^high Treg cells may play a role in the pathogenesis of uveitis in VKH syndrome.