Appearance of Mature 6-Sulfo LacNAc+ Dendritic Cells In Early and Late Engraftment After Allogeneic Stem Cell Transplantation.
Authors: Tuve Sebastian , Mager Konrad , Wehner Rebekka , Bahr Felix , Ölschlegel Uta , Shayegi Nona , Middeke Jan Moritz , Heuchel Conrad , Röllig Christoph , Radke Jörgen , Wermke Martin , Platzbecker Uwe , Schetelig Johannes , Thiede Christian , Ehninger Gerhard , Bornhaeuser Martin , Schmitz Marc 
Published: October 2019

Abstract
Abstract 3720

Background:
Dendritic cells (DCs) are professional antigen-presenting cells which display an extraordinary capacity to induce, sustain and regulate T cell responses. Recently, 6-sulfo LacNAc+ (slan) DCs (formerly termed M-DC8+ DCs) have been described as a major subpopulation of proinflammatory human blood DCs which are principal producers of tumor necrosis factor-alpha and interleukin-12. In addition, it has been demonstrated that slanDCs efficiently induce antigen-specific CD4+ and CD8+ T cells and direct the polarization of naïve CD4+ T lymphocytes into Th1 cells. In the present study, we investigated the reconstitution kinetics of slanDCs after allogeneic stem cell transplantation (aSCT) in comparision to CD1c+ myeloid DCs and plasmacytoid DCs representing two additional major human blood DC subsets.

Material and Methods:
The frequency of slanDCs, CD1c+ myeloid DCs and plasmacytoid DCs in the peripheral blood was quantified by flow cytometry in 70 patients following aSCT at different time points in early engraftment (<30 days post transplantation) and late engraftment (30–100 days post transplantation). To assess the individual DC subsets we used pregating of the HLADR+Lin− subset and antibodies against the following antigens: 6-sulfo LacNAc (slanDCs), BDCA-1 (CD1c+ myeloid DCs) and BDCA-2 (plasmacytoid DCs). Maturation status was determined by analyzing the surface expression of HLADR and CD86.

Results:
(1) Early engraftment (<30 days post transplantation): In the early phase after transplantation CD1c+ myeloid DCs and plasmacytoid DCs show rapid engraftment. These DC subsets are predominant in early engraftment. In contrast, slanDCs only represent a minor proportion of DCs in the first month after transplantation. However, in contrast to CD1c+ myeloid DCs and plasmacytoid DCs which display an immature phenotype, the majority of slanDCs are mature in early engraftment. (2) Late engraftment (>30 days post transplantation): Interestingly, in the late phase post transplantation, the frequency of slanDCs steadily increases and these DCs represent the most abundant DC subpopulation in the second and third month post transplantation. The frequency of CD1c+ myeloid DCs and plasmacytoid DCs remains unchanged. Again, the majority of slanDCs show a mature phenotype in contrast to CD1c+ myeloid DCs and plasmacytoid DCs.

Conclusion:
Whereas the early engraftment phase after aSCT is dominated by CD1c+ myeloid DCs and plasmacytoid DCs, slanDCs represent the most abundant DC subset in the late engraftment phase. Furthermore, in both engraftment phases the majority of slanDCs display a mature phenotype in contrast to CD1c+ myeloid DCs and plasmacytoid DCs. Current studies are focused on functional assays and the role of individual DC populations in acute graft-versus-host disease and graft-versus-leukemia responses in the early and late phase following aSCT.

Disclosures:
Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.