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

被引:40
作者
Zaucha, JM
Zellmer, E
Georges, G
Little, MT
Storb, R
Storer, B
Torok-Storb, B
机构
[1] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA
[2] Univ Washington, Dept Med, Seattle, WA 98109 USA
[3] Univ Washington, Dept Biostat, Seattle, WA 98109 USA
关键词
nonmyeloablative transplants; CD3-depleted; G-CSF; graft facilitating; mixed chimerism;
D O I
10.1053/bbmt.2001.v7.pm11760149
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 whether the 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. Ve 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.
引用
收藏
页码:613 / 619
页数:7
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