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

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

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number4 47-4
Publication statusPublished - 2003 Apr 1
Externally publishedYes

Fingerprint

Therapeutic Uses
Colitis
T-Lymphocytes
Crohn Disease
Interleukin-2
Mucous Membrane
SCID Mice
Adoptive Transfer
Antigen-Presenting Cells
Colon
Therapeutics
Animal Models
Ligands

Keywords

  • Crohn's disease
  • OX40L
  • Therapy
  • Tumor necrosis factor-a

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis. / Totsuka, T.; Kanai, Takanori; Uraushihara, K.; Iiyama, R.; Yamazaki, M.; Akiba, H.; Yagita, H.; Okumura, K.; Watanabe, M.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 284, No. 4 47-4, 01.04.2003.

Research output: Contribution to journalArticle

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, vol. 284, no. 4 47-4.
Totsuka, T. ; Kanai, Takanori ; Uraushihara, K. ; Iiyama, R. ; Yamazaki, M. ; Akiba, H. ; Yagita, H. ; Okumura, K. ; Watanabe, M. / Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2003 ; Vol. 284, No. 4 47-4.
@article{9af26e64ade745c2b9dcfee280bdd084,
title = "Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis",
abstract = "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.",
keywords = "Crohn's disease, OX40L, Therapy, Tumor necrosis factor-a",
author = "T. Totsuka and Takanori Kanai and K. Uraushihara and R. Iiyama and M. Yamazaki and H. Akiba and H. Yagita and K. Okumura and M. Watanabe",
year = "2003",
month = "4",
day = "1",
language = "English",
volume = "284",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 47-4",

}

TY - JOUR

T1 - Therapeutic effect of anti-OX40l and anti-TNF-α MAbs in a murine model of chronic colitis

AU - Totsuka, T.

AU - Kanai, Takanori

AU - Uraushihara, K.

AU - Iiyama, R.

AU - Yamazaki, M.

AU - Akiba, H.

AU - Yagita, H.

AU - Okumura, K.

AU - Watanabe, M.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - 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.

AB - 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.

KW - Crohn's disease

KW - OX40L

KW - Therapy

KW - Tumor necrosis factor-a

UR - http://www.scopus.com/inward/record.url?scp=0037378345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037378345&partnerID=8YFLogxK

M3 - Article

C2 - 12631559

AN - SCOPUS:0037378345

VL - 284

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 47-4

ER -