Inhibition of NKG2D receptor function by antibody therapy attenuates transfer-induced colitis in SCID mice

Eur J Immunol. 2007 May;37(5):1397-406. doi: 10.1002/eji.200636473.


A role for the activating NK-receptor NKG2D has been indicated in several autoimmune diseases in humans and in animal models of type 1 diabetes and multiple sclerosis, and treatment with monoclonal antibodies to NKG2D attenuated disease severity in these models. In an adoptive transfer-induced model of colitis, we found a significantly higher frequency of CD4(+)NKG2D(+) cells in blood, mesenteric lymph nodes, colon, and spleen from colitic mice compared to BALB/c donor-mice. We, therefore, wanted to study the effect of anti-NKG2D antibody (CX5) treatment initiated either before onset of colitis, when the colitis was mild, or when severe colitis was established. CX5 treatment decreased the detectable levels of cell-surface NKG2D and prophylactic administration of CX5 attenuated the development of colitis significantly, whereas a more moderate reduction in the severity of disease was observed after CX5 administration to mildly colitic animals. CX5 did not attenuate severe colitis. We conclude that the frequency of CD4(+)NKG2D(+) cells increase during development of experimental colitis. NKG2D may play a role in the early stages of colitis in this model, since early administration of CX5 attenuated disease severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Colitis / drug therapy*
  • Colitis / immunology*
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Mice
  • Mice, SCID
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / immunology
  • Receptors, Natural Killer Cell
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism


  • Antibodies, Monoclonal
  • Interleukin-2 Receptor alpha Subunit
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell