title: G-CSF-mobilized peripheral blood mononuclear cells added to marrow facilitates engraftment in nonmyeloablated canine recipients: CD3 cells are required.
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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington 98109-1024, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Zaucha
authors.forename: E
authors.initials: E
authors.lastname: Zellmer
authors.forename: G
authors.initials: G
authors.lastname: Georges
authors.forename: M T
authors.initials: MT
authors.lastname: Little
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: B
authors.initials: B
authors.lastname: Storer
authors.forename: B
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D016026:Bone Marrow Transplantation / Q000379:methods*; D017252:CD3 Complex / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage; D004285:Dogs; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000637:transplantation*; D018950:Lipopolysaccharide Receptors; D023421:Models, Animal; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014916:Whole-Body Irradiation
chemical_list: D018952:Antigens, CD34; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D016179:Granulocyte Colony-Stimulating Factor; D016572:Cyclosporine; D009173:Mycophenolic Acid