The role of dendritic cells (DCs) and macrophages in allogeneic hematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft versus host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in hematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft versus host disease (GVHD) tissue-specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs, and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified since day +21, showing median frequencies comparable to healthy donors, a donor origin, and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporine treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing TNF-α upon LPS stimulation. Nonetheless, they were almost undetectable in GVHD tissue-specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out a direct participation of these cells in the majority of the local reactions characterizing GVHD.
Rapid reconstitution of functionally active 6-sulfoLacNAc(+) dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant
COSTANTINI, Claudio;
2014
Abstract
The role of dendritic cells (DCs) and macrophages in allogeneic hematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft versus host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in hematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft versus host disease (GVHD) tissue-specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs, and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified since day +21, showing median frequencies comparable to healthy donors, a donor origin, and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporine treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing TNF-α upon LPS stimulation. Nonetheless, they were almost undetectable in GVHD tissue-specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out a direct participation of these cells in the majority of the local reactions characterizing GVHD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
