Flt3 ligand therapy for recipients of allogeneic bone marrow transplants expands host CD8α+ dendritic cells and reduces experimental acute graft-versus-host disease

Takanori Teshima, Pavan Reddy, Kathleen P. Lowler, Mark A. Kukuruga, Chen Liu, Kenneth R. Cooke, James L.M. Ferrara

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Recent evidence suggests that dendritic cells (DCs) can regulate and amplify immune responses. Flt3 ligand (FL)-derived DC function was tested as a stimulator of allogeneic lymphocytes in vitro and in vivo. Treatment of mice with FL dramatically expanded DC number, but DCs isolated from FL-treated mice (FL DCs) were poor stimulators of allogeneic T-cell responses in vitro. Further activation of FL DCs did not restore their stimulatory ability, and FL DCs did not suppress the stimulation of the allogeneic T cells by normal DCs, FL treatment significantly increased the CD8α+ DC subset, which appeared to be the reason for their poor stimulatory capacity. These observations were confirmed in vivo using a mouse model of acute graft-versus-host disease (GVHD) wherein host DCs play a critical role. FL treatment of recipients before allogeneic bone marrow transplantation dramatically suppressed donor T-cell responses to host antigens, thereby reducing GVHD mortality (P < .01). These data represent a novel strategy that alters host DCs and reduces acute GVHD.

Original languageEnglish
Pages (from-to)1825-1832
Number of pages8
JournalBlood
Volume99
Issue number5
DOIs
StatePublished - 1 Mar 2002
Externally publishedYes

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