Reporting on page 913, Yasunami and colleagues show that activation of natural killer T (NKT) cells triggers rejection of transplanted insulin-producing islet cells in mice. These data suggest a possible way to avoid the early loss of islet cells that has stymied an otherwise promising diabetes treatment.
Insulin-dependent diabetes is caused by destruction of the insulin-producing cells in the pancreas by CD4+ T cells. Transplantation of islet cells is an effective way to restore insulin production, but this therapy requires life-long immunosuppression of the patient. And even with immunosuppression, up to half of the transplanted islet cells are rapidly rejected.
Early islet rejection is associated with the production of inflammatory cytokines such as interferon-γ (IFN-γ), but the cell types involved in IFN-γ production and in islet cell rejection had not been defined. Yasunami and colleagues now place the blame on NKT cells. NKT cells in mice produced IFN-γ in response to islet cell transplantation. This triggered the production of more IFN-γ by graft-infiltrating neutrophils. In the absence of NKT cells, neutrophils or IFN-γ, the islet cells survived.
Multiple injections with the NKT cell–activating compound α-galactosylceramide also protected against islet rejection, consistent with recent reports suggesting that chronic stimulation of NKT cells decreases IFN-γ production. Thus, early inhibition of NKT cells might help protect transplanted islet cells, even before destructive T cells are activated.