Flt3 ligand (FL) treatment of murine donors does not modify graft-versus-host disease (GVHD) but FL treatment of recipients post-bone marrow transplantation accelerates GVHD lethality.
Flt3 ligand (FL) is a hematopoietic cytokine that has been shown to facilitate the expansion of dendritic cells (DCs) and the generation of antitumor immune responses. In addition, the use of FL in mobilizing peripheral blood progenitor cells is being investigated. In the present study, we sought to quantify the influence of FL-treated donor cells on graft-versus-host disease (GVHD). FL treatment resulted in a marked expansion in the absolute number of myeloid- and lymphoid-related DCs and a reduction in the proportion of donor splenic T cells. Irradiated recipients who were given splenocytes from FL-treated donors had reduced GVHD lethality compared with controls due to the infusion of fewer mature T cells. Highly purified T cells from FL-treated donors produced comparable in vitro alloresponses and there was no evidence of a skewing toward T-helper type 1 (interleukin [IL]-2, interferon-gamma) or T-helper type 2 (IL-4, IL-10) cytokine production. The GVHD lethality associated with purified T cells obtained from FL-treated or control donors was comparable. In contrast, FL treatment of recipients resulted in a significant increase in GVHD lethality. Increased lethality was observed even when the infusions of allogeneic T cells and FL were delayed until 3 weeks post-bone marrow transplantation (BMT). Our data indicate that FL treatment of donors does not increase GVHD risk, but treatment of recipients increases GVH lethality even if FL treatment is delayed until later post-BMT.
Blazar
B R
BR
Cancer Center and the Department of Pediatrics, Fairview-University of Minnesota Hospital and Clinics, Minneapolis, USA. blaza001@tc.umn.edu
McKenna
H J
HJ
Panoskaltsis-Mortari
A
A
Taylor
P A
PA
D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology*; D015993:Life Tables; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000494:pharmacology / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D014019:Tissue Donors
D008565:Membrane Proteins; C084881:flt3 ligand protein