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

Clin Exp Immunol. 2012 Apr;168(1):68-74. doi: 10.1111/j.1365-2249.2011.04543.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Behcet Syndrome / immunology*
  • Behcet Syndrome / metabolism
  • Behcet Syndrome / pathology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Interleukin-23 / biosynthesis
  • Interleukin-23 / immunology
  • Interleukin-23 / metabolism
  • Leukocyte Common Antigens / genetics
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Skin / immunology
  • Skin / pathology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology

Substances

  • Interleukin-17
  • Interleukin-23
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • Interferon-gamma
  • Leukocyte Common Antigens