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

PURPOSE. To determine whether infliximab induces the development of Foxp3(+) T regulatory (Treg) cells in patients with Behc, et's disease. METHODS. The subjects were patients with refractory uveitis caused by Behc, et'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. RESULTS. Foxp3 was expressed in a small percentage of CD4(+) T cells (<5%) from healthy subjects and from patients with active uveitis caused by Behc, et'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 TGF beta, and the Treg cells significantly suppressed the activation of bystander T cells in vitro. CONCLUSIONS. Anti-TNF-alpha therapy may be useful for patients with ocular complications of Behc, et's disease who have a decreased percentage of peripheral Treg cells. (Invest Ophthalmol Vis Sci. 2011; 52: 476-484) DOI: 10.1167/iovs.10-5916