AJP - GI Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Gastrointest Liver Physiol 284: G595-G603, 2003. First published January 10, 2003; doi:10.1152/ajpgi.00450.2002
0193-1857/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/4/G595    most recent
00450.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Totsuka, T.
Right arrow Articles by Watanabe, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Totsuka, T.
Right arrow Articles by Watanabe, M.
Vol. 284, Issue 4, G595-G603, April 2003

Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis

T. Totsuka1, T. Kanai1, K. Uraushihara1, R. Iiyama1, M. Yamazaki1, H. Akiba2, H. Yagita2, K. Okumura2, and M. Watanabe1

1 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo 113 - 8519; and 2 Department of Immunology, Juntendo University School of Medicine, Tokyo 113 - 8421, Japan

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-alpha 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-gamma , IL-2, and TNF-alpha production by lamina propria CD4+ T cells. The combination with anti-TNF-alpha MAb further improved the therapeutic effect by abolishing IFN-gamma , IL-2, and TNF-alpha 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-alpha blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

OX40L; tumor necrosis factor-alpha ; Crohn's disease; therapy


This article has been cited by other articles:


Home page
 J. Immunol.Home page
J. R. Maxwell, R. Yadav, R. J. Rossi, C. E. Ruby, A. D. Weinberg, H. L. Aguila, and A. T. Vella
IL-18 Bridges Innate and Adaptive Immunity through IFN-{gamma} and the CD134 Pathway
J. Immunol., July 1, 2006; 177(1): 234 - 245.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
T. Ito, Y.-H. Wang, O. Duramad, T. Hori, G. J. Delespesse, N. Watanabe, F. X.-F. Qin, Z. Yao, W. Cao, and Y.-J. Liu
TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand
J. Exp. Med., November 7, 2005; 202(9): 1213 - 1223.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
N. Dan, T. Kanai, T. Totsuka, R. Iiyama, M. Yamazaki, T. Sawada, T. Miyata, H. Yagita, K. Okumura, and M. Watanabe
Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis
Am J Physiol Gastrointest Liver Physiol, October 1, 2003; 285(4): G754 - G760.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online