Dysregulated donor T cells lead to destruction of host tissues resulting in graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). We investigated the impact of highly purified (>95%) donor CD4(+) invariant natural killer T (iNKT) cells on GVHD in a murine model of allogeneic HCT. We found that low doses of adoptively transferred donor CD4(+) iNKT cells protect from GVHD morbidity and mortality through an expansion of donor CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg). These Treg express high levels of the Ikaros transcription factor Helios and expand from the Treg pool of the donor graft. Furthermore, CD4(+) iNKT cells preserve T cell-mediated graft-versus-tumor (GVT) effects. Our studies reveal new aspects of the cellular interplay between iNKT cells and Treg in the context of tolerance induction after allogeneic HCT and set the stage for clinical translation.
View details for DOI 10.1182/blood-2014-05-576017