title: Excessive CD4+ T cells co-expressing interleukin-17 and interferon-γ in patients with Behçet's disease.
abstract: 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.
authors.affiliation: Department of Immunology and Medicine, St Marianna University School of Medicine, Sugao 2-16-1, Kawasaki, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Shimizu
authors.forename: K
authors.initials: K
authors.lastname: Takai
authors.forename: N
authors.initials: N
authors.lastname: Fujiwara
authors.forename: N
authors.initials: N
authors.lastname: Arimitsu
authors.forename: Y
authors.initials: Y
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Wakisaka
authors.forename: H
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: F
authors.initials: F
authors.lastname: Kaneko
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics; D008297:Male; D008875:Middle Aged; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology
chemical_list: D020381:Interleukin-17; D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens