Dog leukocyte antigen nonidentical unrelated canine marrow grafts: enhancement of engraftment by CD4 and CD8 T cells.
BACKGROUND
Previous studies have demonstrated that most marrow grafts from dog leukocyte antigen (DLA)-mismatched unrelated donors were rejected after 9.2 Gy total body irradiation (TBI), and that graft resistance could be overcome by infusing viable peripheral blood mononuclear cells (PBMCs) in addition to marrow.


METHODS
To investigate the donor cell populations that facilitate engraftment, we determined the minimal dose of PBMCs required to ensure stable engraftment. Nineteen dogs underwent transplantation with DLA-mismatched unrelated marrow and PBMCs in a dose de-escalation study. In subsequent studies, 12 dogs were given selected CD4 or CD8 cells in addition to marrow.


RESULTS
When 3 x 108 PBMC/kg were given in addition to a median of 4 x 108 marrow cells/kg, five of six animals engrafted. At a dose of 1 x 108 PBMC/kg, four of eight animals engrafted, and none of five dogs engrafted at a dose of 3 x 107 PBMC/kg. Accordingly, 12 dogs were given 9.2 Gy TBI, marrow grafts from DLA-mismatched unrelated dogs, and a median of 5.2 x 107 selected CD8 cells/kg or 10.4 x 107 selected CD4 cells/kg corresponding to the number of CD8 or CD4 cells contained in 3 x 108 PBMC/kg. Five of six dogs given CD8 cells and five of six dogs given CD4 cells engrafted.


CONCLUSIONS
Results indicate that at least 3 x 108 unmodified PBMC/kg are needed for stable engraftment of DLA-mismatched unrelated marrow, and that both CD4 and CD8 cell subpopulations are capable of facilitating engraftment.
Panse
Jens P
JP
The Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Bastianelli
Carla
C
Santos
Erlinda B
EB
Schwarzinger
Ilse
I
Raff
Robert F
RF
Storb
Rainer
R
Sandmaier
Brenda M
BM
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004285:Dogs; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed
D006680:HLA Antigens