Dog leukocyte antigen nonidentical unrelated canine marrow grafts: enhancement of engraftment by CD4 and CD8 T cells

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