Induction of Regulatory T Cells by Infliximab in Behçet's Disease

Abstract

To determine whether infliximab induces the development of Foxp3+ T regulatory (Treg) cells in patients with Behçet's disease. The subjects were patients with refractory uveitis caused by Behçet's disease, Vogt-Koyanagi-Harada disease, or ocular toxoplasmosis and healthy volunteers. Purified CD4+ T cells were obtained from patients with uveitis who were treated with colchicine, cyclosporine, or infliximab. Flow cytometry was used to analyze the expression of Foxp3 on CD4+ T cells. Foxp3 was expressed in a small percentage of CD4+ T cells (<5%) from healthy subjects and from patients with active uveitis caused by Behçet's disease, Vogt-Koyanagi-Harada disease, or ocular toxoplasmosis. The percentage of Foxp3+ cells among CD4+ T cells was significantly decreased in patients with active uveitis compared with patients with inactive uveitis in the remission stage. Foxp3 was expressed at a similar level in CD4+ T cells from healthy donors, colchicine-treated patients, and cyclosporine-treated patients, whereas infliximab-treated patients expressed much higher percentages of Foxp3+ cells. Patients who had a high population of Foxp3+ cells during infliximab treatment did not experience any subsequent episodes of acute uveitis. On the other hand, patients with a low population of Foxp3+ cells did experience ocular inflammatory episodes. T cells exposed to infliximab in vitro greatly expressed Foxp3 and produced TGFβ, and the Treg cells significantly suppressed the activation of bystander T cells in vitro. Anti-TNF-α therapy may be useful for patients with ocular complications of Behçet's disease who have a decreased percentage of peripheral Treg cells.