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. CONCLUSION: 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.
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. CONCLUSION: 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.
Authors: E Mimiola; O Marini; O Perbellini; A Micheletti; W Vermi; S Lonardi; C Costantini; E Meneghelli; A Andreini; C Bonetto; A Vassanelli; M Cantini; E Zoratti; D Massi; A Zamo'; A Leso; G Quaresmini; F Benedetti; G Pizzolo; M A Cassatella; C Tecchio Journal: Clin Exp Immunol Date: 2014-10 Impact factor: 4.330
Authors: Ulrich Sommer; Brit Larsson; Sebastian Tuve; Rebekka Wehner; Nick Zimmermann; Michael Kramer; Anja Kloβ; Claudia Günther; Jana Babatz; Renate Schmelz; Stefan Brückner; Johannes Schetelig; Martin Bornhäuser; Knut Schäkel; Michael Philipp Bachmann; Daniela Aust; Gustavo Baretton; Marc Schmitz Journal: Haematologica Date: 2014-03-28 Impact factor: 9.941
Authors: Marco Mielcarek; Anna Yasmine Kirkorian; Robert C Hackman; Jeremy Price; Barry E Storer; Brent L Wood; Marylene Leboeuf; Milena Bogunovic; Rainer Storb; Yoshihiro Inamoto; Mary E Flowers; Paul J Martin; Matthew Collin; Miriam Merad Journal: Transplantation Date: 2014-09-15 Impact factor: 4.939
Authors: Jurjen M Ruben; Hetty J Bontkes; Theresia M Westers; Erik Hooijberg; Gert J Ossenkoppele; Arjan A van de Loosdrecht; Tanja D de Gruijl Journal: Oncoimmunology Date: 2014-07-03 Impact factor: 8.110