FLT3 ligand promotes engraftment of allogeneic hematopoietic stem cells without significant graft-versus-host disease1
作者:
Murad Yunusov,
George Georges,
Rainer Storb,
Peter Moore,
Hans Hagglund,
Verena Affolter,
Marina Lesnikova,
M. Gass,
Marie-Térèse Little,
Michael Loken,
Hilary McKenna,
Barry Storer,
Richard Nash,
期刊:
Transplantation
(OVID Available online 2003)
卷期:
Volume 75,
issue 7
页码: 933-940
ISSN:0041-1337
年代: 2003
出版商: OVID
数据来源: OVID
摘要:
Background.Graft-versus-host (GVH) reactions contribute to stable engraftment of allogeneic hematopoietic stem cell transplants. It was hypothesized that the in vivo expansion of recipient dendritic cells (DC) with the administration of ligand for Flt3 (FL) could promote allogeneic engraftment after reduced-intensity conditioning by enhancing the GVH effect.Methods.FL was first administered to three nonirradiated healthy dogs for 13 days at a dosage of 100 &mgr;g/kg/day. Next, nine dogs received 4.5 Gy total-body irradiation (TBI) and unmodified marrow grafts from dog leukocyte antigen (DLA)-identical littermates without posttransplant immunosuppression. FL was administered to the recipients at a dosage of 100 &mgr;g/kg/day from day −7 until day +5.Results.In normal dogs, FL produced significant increases in monocytes (CD14+) and neutrophils in the peripheral blood, a marked increase in CD1c+cells with DC-type morphology in lymph nodes, and increased alloreactivity of third-party responders to peripheral blood mononuclear cells in mixed lymphocyte reactions (P<0.001). Sustained engraftment was observed in eight of nine (89%) FL-treated dogs compared with 14 of 37 (38%) controls (P=0.02, logistic regression). All engrafted FL-treated dogs became stable complete (n=2) or mixed (n=6) hematopoietic chimeras without significant graft-versus-host disease (GVHD). Recipient chimeric dogs (n=4) were tolerant to skin transplants from their marrow donors but rejected skin grafts from unrelated dogs within 7 to 9 days (median, 8 days).Conclusions.In this study, the authors showed that FL administered to recipients promotes stable engraftment of allogeneic marrow from DLA-identical littermates after 4.5 Gy TBI without significant GVHD.
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