CD41 invariant natural killer T cells protect from murine GVHD lethality through expansion of donor CD41CD251FoxP31 regulatory T cells

Abstract

Dysregulated donor T cells lead to destruction of host tissues resulting in graftversus- host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (95%) donor CD41 invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD41 iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD41CD251FoxP31 regulatory T cells (Tregs). These Tregs express high levels of the Ikaros transcription factor Helios and expand from the Treg pool of the donor graft. Furthermore, CD41 iNKT cells preserve T-cell-mediated graft-versus-tumor effects. Our studies reveal new aspects of the cellular interplay between iNKT cells and Tregs in the context of tolerance induction after allogeneic HCT and set the stage for clinical translation. (Blood. 2014;124(22):3320-3328).