Augmentation of donor bone marrow engraftment in histoincompatible murine recipients by granulocyte/macrophage colony-stimulating factor.
T cell depletion of donor bone marrow can prevent graft v host disease (GVHD) in human and murine marrow graft recipients. However, engraftment in the recipient may be compromised as a consequence of donor marrow T cell depletion. The effect of recombinant murine granulocyte/macrophage colony-stimulating factor (rmu GM-CSF) on engraftment and hematologic reconstitution was evaluated in a murine allogeneic bone marrow transplantation (BMT) model involving T cell depletion of marrow. Before transplantation into irradiated mice differing at major and minor histocompatibility loci, rmu GM-CSF was preincubated with T cell-depleted donor marrow. When low degrees of engraftment were noted in control recipients, treatment of donor marrow with high concentrations of rmu GM-CSF led to enhanced engraftment. Ex vivo donor graft incubation with rmu GM-CSF or a single in vivo injection of rmu GM-CSF were both effective means of promoting engraftment. When the engraftment rate in control recipients was high, rmu GM-CSF did not have an identifiable effect. Only slight increases in hematologic recovery were detected regardless of the rate of engraftment. Neither post-BMT survival nor marrow stem cell capacity was affected by rmu GM-CSF incubation. Furthermore, growth factor administration did not have a significant effect on the incidence of GVHD in recipients of non-T cell-depleted bone marrow splenocyte preparations. In vitro natural killer-mediated target cell lysis was not altered by incubation of effector cells with rmu GM-CSF. These results demonstrate the potential of ex vivo rmu GM-CSF treatment of donor marrow to facilitate engraftment across extensive histo-compatibility barriers.
Blazar
B R
BR
Department of Pediatrics, University of Minnesota Hospital, Minneapolis 55455.
Widmer
M B
MB
Soderling
C C
CC
Urdal
D L
DL
Gillis
S
S
Robison
L L
LL
Vallera
D A
DA
D000818:Animals; D016026:Bone Marrow Transplantation; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor