The Role of Invariant NKT Cells in Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure for a number of hematological malignancies including leukemia and lymphoma. However, the anti-leukemia (graft-versus-leukemia, GVL) effect mediated by T cells transferred to the host with the allograft is often negated by the graft-versus-host (GVH) reaction imparted by the same cells. Acute graft-versus-host disease (aGVHD), an allogeneic reaction triggered in response to minor and major histocompatibility antigen disparities between donor and recipient, remains the main source of morbidity and mortality in T-cell-replete allogeneic HSCT. Here we review the biological properties, the pre-clinical work, and the recent clinical observations suggesting that invariant natural killer (iNK) T cells, a CD1d-restricted subset of immunoregulatory T cells, are important regulators of GVH and GVL reactions. Further, we outline strategies for manipulating iNKT cells to translate their therapeutic promise into clinical benefit in the context of allogeneic HSCT.