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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4156-4163
Number of pages8
JournalJournal of Immunology
Volume171
Issue number8
StatePublished - Oct 15 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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  • Cite this

    Kanai, T., Totsuka, T., Uraushihara, K., Makita, S., Nakamura, T., Koganei, K., Fukushima, T., Akiba, H., Yagita, H., Okumura, K., Machida, U., Iwai, H., Azuma, M., Chen, L., & Watanabe, M. (2003). Blockade of B7-H1 suppresses the development of chronic intestinal inflammation. Journal of Immunology, 171(8), 4156-4163.