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

Citation
Br. Blazar et al., 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, BIOL BLOOD, 7(4), 2001, pp. 197-207
Citations number
65
Categorie Soggetti
Hematology
Journal title
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
ISSN journal
10838791 → ACNP
Volume
7
Issue
4
Year of publication
2001
Pages
197 - 207
Database
ISI
SICI code
1083-8791(2001)7:4<197:FL(TOM>2.0.ZU;2-M
Abstract
Flt3 ligand (FL) is a hematopoietic cytokine that has been shown to facilit ate 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 dise ase (GVHD). FL treatment resulted in a marked expansion in the absolute num ber 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 du e 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-heher type 1 (interleukin [IL]-2, interferon -gamma) or T-helper type 2 (IL-4, IL-10) cytokine production. The GVHD leth ality 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 w eeks post-bone marrow transplantation (BMT). Our data indicate that FL trea tment of donors does not increase GVHD risk, but treatment of recipients in creases GVH lethality even if FL treatment is delayed until later post-BMT.