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
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
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.