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

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.