Reconstitution of 6-sulfo LacNAc dendritic cells after allogeneic stem-cell transplantation.
BACKGROUND
Infections and acute graft-versus-host disease (GvHD) represent major complications of allogeneic stem-cell transplantation (SCT). Dendritic cells (DCs) display an extraordinary capacity to induce innate and adaptive immune responses. Therefore, they play a crucial role in the elimination of pathogens and in the pathogenesis of acute GvHD. 6-Sulfo LacNAc DCs (slanDCs) are a major subpopulation of human blood DCs with a high proinflammatory capacity. We investigated for the first time the reconstitution of slanDCs in the blood of patients after SCT and the modulation of their frequency by bacterial infection, cytomegalovirus (CMV) reactivation, and acute GvHD.


METHODS
The frequency of slanDCs, CD1c myeloid DCs (mDCs), and plasmacytoid DCs (pDCs) in the peripheral blood was quantified by flow cytometry in 80 patients after SCT. To assess individual DC subsets, we used pregating of the HLADRLin subset and antibodies against slanDCs, blood DC antigen 1 (CD1c mDCs), and blood DC antigen 2 (pDCs).


RESULTS
SlanDCs showed the slowest reconstitution in the first month after SCT compared with CD1c mDCs and pDCs. Interestingly, in the second and third months after SCT, their percentage steadily increased, and slanDCs were the most abundant DC subset. In addition, we observed a markedly reduced frequency of slanDCs in the blood of patients with bacterial infection, CMV reactivation, or severe acute GvHD. Furthermore, slanDCs showed the most prominent reduction after steroid treatment of acute GvHD.


CONCLUSIONS
These results indicate that SCT-associated complications such as bacterial infection, CMV reactivation, and acute GvHD can significantly modulate the frequency of slanDCs.
Department of Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
Konrad
K
Mager
Rebekka
R
Wehner
Felix
F
Bahr
Uta
U
Oelschlägel
Uwe
U
Platzbecker
Martin
M
Wermke
Nona
N
Shayegi
Jan Moritz
JM
Middeke
Jörgen
J
Radke
Christoph
C
Röllig
Johannes
J
Schetelig
Christian
C
Thiede
Gerhard
G
Ehninger
Marc
M
Schmitz
Martin
M
Bornhäuser
Sebastian
S
Tuve
D000208:Acute Disease; D056704:Adaptive Immunity / Q000276:immunology; D000328:Adult; D000368:Aged; D000606:Amino Sugars / Q000378:metabolism*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013256:Steroids / Q000627:therapeutic use; D014184:Transplantation, Homologous; D055815:Young Adult
C467438:6-sulfo-LacNac; D000606:Amino Sugars; D001323:Autoantibodies; D013256:Steroids