Fast appearance of donor dendritic cells in human skin: dynamics of skin and blood dendritic cells after allogeneic hematopoietic cell transplantation.
BACKGROUND
Both number and origin (donor vs. host) of dendritic cells (DC) are associated with acute graft-versus-host disease (aGvHD), relapse and graft failure after human allogeneic hematopoietic cell transplantation (aHCT).


METHODS
We prospectively and simultaneously investigated skin and blood DC subtypes, their donor/recipient origin, and the correlation of DC reconstitution kinetics with treatment, clinical outcome, and incidence of aGvHD in patients undergoing aHCT.


RESULTS
A significant reduction of skin and a marked decrease of blood DC were observed in patients compared to healthy volunteers. A dominant donor chimerism of migratory Langerhans cells (LC) and dermal-dendritic-cells (DDC) was detected even early after transplantation, and developed independently from chemotherapy regimen, graft manipulation or time point after transplantation. Before start of the therapy patients showed significantly decreased numbers of peripheral blood CD123+ preDC2, whereas CD11c+ preDC1 numbers appeared to be diminished, but were statistically indistinguishable from controls. Host derived pB preDC were virtually absent following aHCT. After a further reduction in cell number around day 56 both preDC subtypes reconstituted and stabilized to pretransplant numbers by day 112. Occurrence of aGvHD and its treatment diminished numbers of both preDC subtypes. Furthermore conditioning therapy with Alemtuzumab apparently affected reconstitution of both preDC subsets negatively.


CONCLUSIONS
Given that induction of GvHD in humans is as host DC dependent as in mouse models, investigation of DC chimerism and number at different sites and especially in GvHD target organs might provide important insights into the pathogenesis of the main obstacle of aHCT.
Auffermann-Gretzinger
Susanne
S
Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus der Technischen Universität, Fetscherstrasse 74, D-01307 Dresden, Germany. Susanne.gretzinger@uniklinikum-dresden.de
Eger
Lars
L
Bornhäuser
Martin
M
Schäkel
Knut
K
Oelschlaegel
Uta
U
Schaich
Markus
M
Illmer
Thomas
T
Thiede
Christian
C
Ehninger
Gerhard
G
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D018949:Antigens, CD1 / Q000032:analysis; D002452:Cell Count; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012867:Skin / Q000473:pathology*; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018949:Antigens, CD1; C419393:CD1a antigen; D000074323:Alemtuzumab