Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behcet Disease Uveitis

PURPOSE. To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behcet disease (BD) patients with uveitis. METHODS. Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3(+)CD4(+)Foxp3(+) and CD3(+)CD4(+)IL17A(+), respectively. Th17 RAR-related orphan receptor (ROR)gamma t mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4(+)T cells and monocytes. RESULTS. Treg and Th17 cell frequencies and Th17 ROR gamma t expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-gamma, and TNF-alpha concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 ROR gamma t expression, Treg and Th17 cell cytokine production, and TLR expression by CD4(+)T cells and monocytes. CONCLUSIONS. Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4(+)T cells and monocytes.