iNKT cells and hematopoietic stem cell transplantation: Two-phase activation of iNKT cells may improve outcome.

Invariant natural killer T cells (iNKT) produce large amounts of different cytokines which can influence differentiation, polarization and activation of immune cells, particularly NK and T cells. iNKT have been shown to suppress GvHD and promote anti-tumor and anti-pathogen immunity. There are highly specific and safe synthetic ligands such as alpha-galactosylceramide (α-GalCer) and C20:2 which activate iNKT cells toward relatively Th1 and Th2 pathways, respectively. Bone marrow transplantation (BMT) or 'hematopoietic stem cell transplantation' (HSCT) is effective for leukemia and lymphoma through 'graft-versus-leukemia' (GVL) immunity. However, frequent serious complications include graft-versus-host-disease (GVHD), opportunistic infections and relapse. Both GVHD and GVL are mediated by T cells. Manipulating iNKT by different lipid analogues in early and late phases after transplantation may suppress GVHD and graft rejection and enhance GVL effect, as well as resistance to opportunistic infections and so, could be a novel and effective strategy for improving HSCT outcome.