Requirement for natural killer T (NKT) cells in the induction of allograft tolerance

In this study, we investigated the role of V alpha 14 natural killer T(NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and V alpha 14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not V alpha 14 NKT cell-deficient mice. Adoptive transfer with V alpha 14 NKT cells restored long-term acceptance of allografts in V alpha 14 NKT cell-deficient mice. The critical role of V alpha 14 NKT cells to mediate immunosuppression was also observed in vitro in mixed lymphocyte cultures in which lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions were blocked. Experiments using IL-4- or IFN-gamma -deficient mice suggested a critical contribution of IFN-gamma to the V alpha 14 NKT cell-mediated allograft acceptance in vivo. These results indicate a critical contribution of Va14 NKT cells to the induction of allograft tolerance and provide a useful model to investigate the regulatory role of V alpha 14 NKT cells in various immune responses.