Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitis

Y. Ito, T. Kanai, T. Totsuka, R. Okamoto, K. Tsuchiya, Y. Nemoto, A. Yoshioka, T. Tomita, T. Nagaishi, N. Sakamoto, T. Sakanishi, K. Okumura, H. Yagita, M. Watanabe

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


It has been recently demonstrated that NKG2D is an activating costimulatory receptor on natural killer (NK) cells, natural killer T (NKT) cells, activated CD8+ T cells, and γδ T cells, which respond to cellular stress, such as inflammation, transformation, and infection. Here we show that intestinal inflammation in colitic SCID mice induced by adoptive transfer of CD4+CD45RBhigh T cells is characterized by significant increase of CD4+NKG2D+ T cells and constitutive expression of NKG2D ligands, such as H60, Mult-1, and Rae-1, by lamina propria CD11c + dendritic cells. Furthermore, treatment with nondepleting and neutralizing anti-NKG2D MAb after transfer of CD4+CD45RB high T cells into SCID mice significantly suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of IFN-γ by lamina propria CD4+ T cells. These findings demonstrate that NKG2D signaling pathway is critically involved in CD4 + T cell-mediated disease progression and suggest a new therapeutic target for inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)G199-G207
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number1
Publication statusPublished - 2007
Externally publishedYes


  • CD4 T cells
  • Chronic colitis
  • Inflammatory bowel disease
  • NKG2D

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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