Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

Abstract

SummaryThe role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic 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 haematopoietic 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 from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, 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 the direct participation of these cells in the majority of the local reactions characterizing GVHD.

6-Sulfo LacNAc (Slan) as a Marker for Non-classical Monocytes

“…G-CSF treatment can increase the number of slan+ monocytes (75, 76) and this is in line with earlier studies that suggested an increase of CD16 on total blood monocytes after G-CSF (77).…”

slan+ Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP

“…Based on in situ analysis of lymph node sections of DLBCL, we could detect a population of smaller slan þ cells, with monocytoid morphology. This slan þ population was localized within and around the high endothelial venules, suggesting recent cell immigration from the blood, fueled by an increased marrow output (6). Accordingly, slan þ monocytes in patients with DLBCL are significantly increased as compared with HDs.…”

“…Importantly, based on their highly specific reactivity to the very stable slan antigen, slan þ cells can be detected in tissues (including archival material) by antibodies known as DD1, DD2, and M-DC8 (1). To date, slan þ cells have been detected in inflamed tissues of patients affected by Crohn disease, rheumatoid arthritis, psoriasis, acute intestinal GVHD samples, as well as in reactive tonsils and Peyer patches (1,3,5,6). Although the type of differentiation fate of slan þ monocytes in various tissues remains to be established, we have demonstrated that slan þ cells isolated from human tonsils, as well as slan þ monocytes cultured with tonsil-derived medium, show unequivocal terminal differentiation to DCs (5).…”

Current Concepts on 6-sulfo LacNAc Expressing Monocytes (slanMo)

“…During the first month after allogeneic stem cell transplantation slanMo showed slow reconstitution in blood compared to cDCs and pDCs (74), however, a steady increase in the frequency of slanMo has been observed in the 2nd and 3rd month after post-transplantation (75, 76). The slow reconstitution of slanMo after bone marrow transplantation as observed in this study is reflected by reports on non-classical monocytes demonstrating the same slow reconstitution in blood (18).…”