Hyperexpression of Inducible Costimulator and Its Contribution on Lamina Propria T Cells in Inflammatory Bowel Disease

Toshiro Sato, Takanori Kanai, Mamoru Watanabe, Atsushi Sakuraba, Susumu Okamoto, Takaaki Nakai, Akira Okazawa, Nagamu Inoue, Teruji Totsuka, Motomi Yamazaki, Richard A. Kroczek, Tsuneo Fukushima, Hiromasa Ishii, Toshifumi Hibi

研究成果: Article査読

40 被引用数 (Scopus)

抄録

Background & Aims: To investigate the role of inducible costimulator (ICOS), a new member of the CD28 family involved in regulation of T-cell activation and chronic intestinal inflammation, we assessed its expression and functional role in patients with inflammatory bowel disease (IBD). Methods: Expression of ICOS, CD28, and cytotoxic T-lymphocyte antigen (CTLA) 4 on intestinal lamina propria mononuclear cells (LPMC) from patients with ulcerative colitis (UC), Crohn's disease (CD), and normal controls was determined using flow cytometry and immunohistochemistry. Expressions of the ICOS ligand, B7h, on lamina propria B cells, macrophages, and epithelial cells (EC) in the intestinal mucosa were also determined using flow cytometry. The functional costimulatory effect of ICOS on LPMC was assessed by the proliferative response and cytokine production. Results: CD4+ LPMC expressing ICOS was significantly increased in the inflamed mucosa of IBD patients but not in inflammatory or normal controls. B7h was also significantly up-regulated on B cells, macrophages, and EC in inflamed mucosa of IBD patients. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher compared with those of anti-CD3 monoclonal antibody (mAb) alone. Anti-CD3/ICOS-stimulated-LPMC from UC secreted significantly increased amounts of interleukin (IL)-5 among the 3 groups. In contrast, anti-CD3/ICOS-stimulated-LPMC from CD secreted significantly increased amounts of interferon (IFN)-γ in the presence of IL-12. Conclusions: Highly expressed ICOS in activated CD4+ LPMC of IBD patients contributes to the dysregulated immune responses in IBD. Because ICOS hyperexpression was limited to inflammatory sites in IBD patients, ICOS would be a feasible therapeutic target for the treatment of IBD.

本文言語English
ページ(範囲)829-839
ページ数11
ジャーナルGastroenterology
126
3
DOI
出版ステータスPublished - 2004 3

ASJC Scopus subject areas

  • 肝臓学
  • 消化器病学

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