Islet allograft tolerance in the absence of invariant natural killer T cells

The invariant NKT cells are involved in both immunity and immune tolerance. However, their roles in transplant models remain controversial. We studied the role of NKT cells in the allograft response using two different strains of NKT deficient mice (CD1d−/− and Jα18−/− mice), and found that CD1d−/− and Jα18−/− mice rejected islet allografts with a similar kinetics as wild type B6 mice. Treatment of CD1d−/− and Jα18−/− mice with donor specific transfusion and anti-CD154 induced donor specific tolerance, which was identical to similarly treated wt B6 mice. The islet allograft tolerance requires Foxp3+ Tregs. In the periphery, Foxp3+ Tregs in CD1d−/−, Jα18−/−, and wt B6 mice were comparable both phenotypically and functionally. In addition, CD1d−/− and Jα18−/− CD4+ T cells (non-Tregs) could be readily converted to Foxp3+ Tregs by TGF-β in vitro. Our data suggest that islet allograft tolerance can be successfully established without invariant NKT cells.

► Allograft tolerance can be established in the absence of NKT cells. ► Tolerance in this model is dependent on Foxp3+ Tregs. ► The role of NKT cells may be highly conditional in transplant settings.