Shaping of iNKT cell repertoire after unrelated cord blood transplantation

Invariant natural killer T (iNKT) cells have a pivotal role in immune regulation, tumor surveillance, and the induction of allograft tolerance. In this report, we analyze the recovery of iNKT cells after unrelated cord blood transplantation (UCBT) of adult patients with high-risk acute myeloid leukemia. We found that iNKT cells were reconstituted within 1 month after UCBT, at the same time as NK cells and before conventional T cells. These iNKT cells displayed a unique primed/central memory CD4+CD45RO+CCR7+CD62L+ phenotype soon after the transplant. Interestingly, the functional competence of these cells was poor, except for their high GM-CSF production capacity. However, this post-graft functionally immature state was transient and all of the patients tested had fully functional iNKT cells 3 to 6 months post-UCBT and high cytolytic capacity for destroying primary CD1d+ myeloid blast cells. Our results raise the possibility that iNKT cells might play a key role in graft-versus-leukemia activity after UCBT.