Abstract
A recent approach of hematopoietic stem cell (HSC) transplantation from haploidentical donors “mobilized” with G-CSF is based on the selective depletion of αβ T and B lymphocytes from the graft. Through this approach, the patient receives both HSC and mature donor-derived effector cells (including NK cells), which exert both anti-leukemia activity and protection against infections. We previously showed that donor HSC mobilization with G-CSF results in accumulation in the graft of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), capable of inhibiting in vitro the anti-leukemia activity of allogeneic NK cells. Here, we performed a detailed gene expression analysis on NK cells and PMN-MDSCs both derived from mobilized graft. Cytotoxicity assays and real time PCR arrays were performed in NK cells. Microarray technology followed by bioinformatics analysis was used for gene expression profiling in PMN-MDSCs. Results indicate that NK cells from the graft have a lower cytolytic activity as compared to those from non-mobilized samples. Further, mobilized PMN-MDSCs displayed a peculiar transcriptional profile distinguishing them from non-mobilized ones. Differential expression of pro-proliferative and immune-modulatory genes was detected in mobilized PMN-MDSCs. These data strengthen the concept that G-CSF-mobilized PMN-MDSCs present in the graft display unique molecular characteristics, in line with the strong inhibitory effect on donor NK cells.
Highlights
Allogeneic hematopoietic stem cell transplantation (HSCT) is a lifesaving treatment for children with both malignant and nonmalignant severe disorders
We showed that, in HSCT, donor HSC mobilization with G-CSF induces the accumulation of PMNMDSCs in peripheral blood (PB) and, in the graft and that these cells are capable of inhibiting in vitro the anti-leukemia cytolytic activity of donor-derived mature NK cells
We performed a detailed gene expression analysis on both NK cells and PMNMDSCs derived from apheresis after mobilization with G-CSF
Summary
Allogeneic hematopoietic stem cell transplantation (HSCT) is a lifesaving treatment for children with both malignant and nonmalignant severe disorders. In an attempt to overcome these severe complications, a novel method of graft manipulation based on the specific depletion of ab T lymphocytes (responsible of graft-versus-host disease; GvHD) and B cells (in order to prevent Epstein–Barr virus-related posttransplant lymphoproliferative disorders), has been more recently introduced [6, 7]. Through this new approach, the patient receives HSCs and high numbers of cells of the innate immunity (including mature NK cells, gd T lymphocytes and different myeloid cells), some of which may rapidly exert antileukemia activity (graft-versus-leukemia; GvL) and early protection against infections. Infused mature donor NK cells can promptly exert a GvL effect [8,9,10,11,12]
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