Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis

T. Totsuka, T. Kanai, K. Uraushihara, R. Iiyama, M. Yamazaki, H. Akiba, H. Yagita, K. Okumura, M. Watanabe

研究成果: Article

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Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-α MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4+ T cell infiltration in the colon and suppressed IFN-γ IL-2, and TNF-α production by lamina propria CD4+ T cells. The combination with anti-TNF-α MAb further improved the therapeutic effect by abolishing IFN-γ, IL-2, and TNF-α production by lamina propria CD4+ T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-α blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

元の言語English
ページ(範囲)G595-G603
ジャーナルAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
284
発行部数4 47-4
DOI
出版物ステータスPublished - 2003 4 1

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Totsuka, T., Kanai, T., Uraushihara, K., Iiyama, R., Yamazaki, M., Akiba, H., Yagita, H., Okumura, K., & Watanabe, M. (2003). Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis. American Journal of Physiology - Gastrointestinal and Liver Physiology, 284(4 47-4), G595-G603. https://doi.org/10.1152/ajpgi.00450.2002