G-CSF-mobilized peripheral blood mononuclear cells added to marrow facilitates engraftment in nonmyeloablated canine recipients: CD3 cells are required

Biol Blood Marrow Transplant. 2001;7(11):613-9. doi: 10.1053/bbmt.2001.v7.pm11760149.

Abstract

Stable mixed donor/host hematopoietic chimerism can be uniformly established in dogs conditioned with 200 cGy TBI before dog leukocyte antigen (DLA)-identical marrow transplantation and immunosuppressed with a short course of mycophenolate mofetil (MMF) and cyclosporine (CSP) after the transplantation. A further decrease in the TBI dose to 100 cGy or the elimination of MMF in this model results in graft rejection. Here we asked whetherthe addition of G-CSF-mobilized peripheral blood mononuclear cells (G-PBMC) to marrow grafts would enhance donor engraftment in dogs conditioned with 100 cGy TBI and given postgrafting immunosuppression with CSP alone. Using this model, 7 of 9 dogs given only marrow cells rejected their grafts within 8 to 17 weeks after transplantation. In contrast, the addition of unmodified G-PBMC to marrow grafts resulted in stable mixed donor/host chimerism in 5 of 8 dogs studied (P = .06). However, addition of the CD3-depleted fraction of G-PBMC, which contained both CD34 cells and CD14 cells, resulted in engraftment in only 1 of 7 recipients. We conclude that adding G-PBMC to marrow grafts replaced the requirement of MMF and 100 cGy of TBI, and that CD3 cells were required to facilitate engraftment of marrow cells in DLA-identical recipients, whereas the additional CD34 cells present in G-PBMC were not sufficient for this effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD34
  • Bone Marrow Transplantation / methods*
  • CD3 Complex* / blood
  • Cyclosporine / administration & dosage
  • Dogs
  • Graft Survival
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematopoietic Stem Cell Mobilization / methods*
  • Immunosuppressive Agents / administration & dosage
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / transplantation*
  • Lipopolysaccharide Receptors
  • Models, Animal
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Transplantation Chimera
  • Transplantation Conditioning / methods*
  • Whole-Body Irradiation

Substances

  • Antigens, CD34
  • CD3 Complex
  • Immunosuppressive Agents
  • Lipopolysaccharide Receptors
  • Granulocyte Colony-Stimulating Factor
  • Cyclosporine
  • Mycophenolic Acid