Influence of human recombinant interferon-α2a (rhIFN-α2a) on altered lymphocyte subpopulations and monocytes in Behçet's disease

Objective. In Behçet's disease (BD), several abnormalities of lymphocyte subpopulations have been described. Standard treatment comprises immunosuppressive drugs. We successfully treated 50 patients with ocular BD with interferon-α2a (IFN-α2a) (response rate 92%), although this is counterintuitive because IFN-α is immunostimulatory and can sometimes even induce autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. The aim of the present study was to elucidate the immunomodulatory effects that IFN-α might exert on peripheral blood mononuclear cells (PBMC) in BD by examining changes in the distribution of lymphocyte subpopulations under IFN-α2a treatment. Methods. Fourteen patients with ocular BD were evaluated before and at weeks 4 and 24 of IFN-α treatment and compared with 10 healthy controls. PBMC were stained with monoclonal antibodies and measured by flow cytometry. Results. Compared with the controls there is a significant elevation of monocytes (CD14⁺), CD8⁺/γδ T cells, CD3⁺/γδ T cells, natural killer (NK) cells (CD56⁺/CD16⁺) and activated/regulatory T cells (CD4⁺/CD25⁺ and CD8⁺/CD25⁺) in patients with active BD before treatment with IFN-α2a. Numbers of naïve T cells (CD8⁺/CD45⁺RA⁺/RO^-, CD4⁺/CD45⁺RA⁺/RO^-) were significantly lower. Under therapy, NK cells, CD8⁺/γδ T cells and CD3⁺/γδ T cells decreased significantly, whereas B cells increased. The previously reduced expression of HLA class I on monocytes in HLA-B51-positive patients rose to levels comparable to HLA-B51-negative patients. Conclusion. These results implicate the participation of NK cells and γδ T cells, especially CD8⁺/γ δ T cells, in the pathogenesis of BD and may explain one mechanism by which IFN-α2a exerts therapeutic effects. Alternatively, they may result indirectly from remission induction by IFN-α2a. The reduced expression of HLA class I on monocytes in HLA-B51-positive patients might reflect an impaired expression of and antigen presentation by HLA-B51.