Blockade of B7-H1 suppresses the development of chronic intestinal inflammation

Takanori Kanai, Teruji Totsuka, Koji Uraushihara, Shin Makita, Tetsuya Nakamura, Kazutaka Koganei, Tsuneo Fukushima, Hisaya Akiba, Hideo Yagita, Ko Okumura, Utako Machida, Hideyuki Iwai, Miyuki Azuma, Lieping Chen, Mamoru Watanabe

研究成果: Article査読

139 被引用数 (Scopus)

抄録

A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested that its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation and cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 and B7-DC interaction in the development of colitis. We first examined the expression profiles of PD-1 and its ligands in both human inflammatory bowel disease and a murine chronic colitis model induced by adoptive transfer of CD4 +CD45RBhigh T cells to SCID mice. Second, we assessed the therapeutic potential of neutralizing anti-B7-H1 and/or B7-DC mAbs using this colitis model. We found significantly increased expression of PD-1 on T cells and of B7-H1 on T, B, and macrophage/DCs in inflamed colon from both inflammatory bowel disease patients and colitic mice. Unexpectedly, the administration of anti-B7-H1, but not anti-B7-DC, mAb after transfer of CD4 +CD45RBhigh T cells suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced the production of IFN-γ, IL-2, and TNF-α, but not IL-4 or IL-10, by lamina propria CD4+ T cells. These data suggest that the interaction of PD-1/B7-H1, but not PD-1/B7-DC, might be involved in intestinal mucosal inflammation and also show a possible role of interaction between B7-H1 and an as yet unidentified receptor for B7-H1 in inducing T cell activation.

本文言語English
ページ(範囲)4156-4163
ページ数8
ジャーナルJournal of Immunology
171
8
DOI
出版ステータスPublished - 2003 10 15
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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