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.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Publication status||Published - 2007|
- CD4 T cells
- Chronic colitis
- Inflammatory bowel disease
ASJC Scopus subject areas
- Physiology (medical)