Invariant natural killer T (iNKT) cells can experimentally dissociate GVL from graftversus-host-disease (GVHD). Their role in human conventional allogeneic hematopoietic stem cell transplantation (HSCT) is unknown. Here, we analyzed the post-HSCT recovery of iNKT cells in 71 adult allografted patients. Results were compared with conventional T-and NK-cell recovery and correlated to the occurrence of GVHD, relapse, and survival. We observed that posttransplantation iNKT cells, likely of donor origin, recovered independently of T and NK cells in the first 90 days after HSCT and reached greater levels in recipient younger than 45 years (P ‫؍‬ .003) and after a reducedintensity conditioning regimen (P ‫؍‬ .03). Low posttransplantation iNKT/T ratios (ie, < 10 ؊3 ) were an independent factor associated with the occurrence of acute GVHD (aGVHD; P ‫؍‬ .001). Inversely, reaching iNKT/T ratios > 10 ؊3 before day 90 was associated with reduced nonrelapse mortality (P ‫؍‬ .009) without increased risk of relapse and appeared as an independent predictive factor of an improved overall survival (P ‫؍‬ .028). Furthermore, an iNKT/T ratio on day 15 > 0.58 ؋ 10 ؊3 was associated with a 94% risk reduction of aGVHD. These findings provide a proof of concept that early postallogeneic HSCT iNKT cell recovery can predict the occurrence of aGVHD and an improved overall survival. (Blood. 2012;120(10):2144-2154)

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Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34(+) cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34(+) monocytes in peripheral blood CD34(+) cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD.