Excessive CD4+ T cells co‐expressing interleukin‐17 and interferon‐γ in patients with Behçet's disease

Summary Excessive T helper type 1 (Th1) cell activity has been reported in Behçet's disease (BD). Recently, association of Th17 cells with certain autoimmune diseases was reported, and we thus investigated circulating Th17 cells in BD. CD4+CD45RO– (naive) T cells were cultured with Th0‐, Th1‐, Th2‐ and Th17‐related cytokines and antibodies, and their mRNA was studied by real‐time polymerase chain reaction (PCR). When naive CD4+ T cells were cultured with Th1‐ and Th17‐related cytokines, interferon (IFN)‐γ mRNA and interleukin (IL)‐17 mRNA were up‐regulated, respectively, in BD patients. Naive CD4+ T cells cultured in a Th17 cell‐inducing condition expressed IL‐23 receptor (IL‐23R) mRNA excessively. IL‐17 mRNA expression was induced only when naive CD4+T cells were cultured in the presence of IL‐23. CD4+ T cells cultured with Th17 cytokines expressed excessive RAR‐related orphan receptor C (RORC) mRNA. Using intracellular cytokine staining, we found that CD45RO+(memory) CD4+ T cells producing IL‐17 and IFN‐γ simultaneously were increased significantly. Memory CD4+ T cells producing IFN‐γ but not IL‐17 decreased profoundly in BD patients. CD4+ T cells producing IL‐17 and IFN‐γ simultaneously were found in BD skin lesions. Collectively, we found excessive CD4+ T cells producing IL‐17 and IFN‐γ (Th1/Th17) cells in patients with BD, and possible involvement of IL‐23/IL‐23R pathway for the appearance of excessive Th1/Th17 cells.