RESISTANCE TO UNRELATED, DLA-NONIDENTICAL CANINE MARROW GRAFTS IS UNRESTRICTED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX

Dogs undergoing rejection of unrelated, dog leukocyte antigen (DLA)-no nidentical marrow grafts show an increase in mononuclear cell counts i n the peripheral blood at 1 week after transplant. Cells are of host o rigin and express phenotypic and morphologic characteristics of large granular lymphocytes (LGLs). LGLs from rejecting dogs suppress in vitr o growth of donor marrow colony-forming units-granulocyte/macrophage ( CFU-GM) and have natural killer (NK) cell activity. The current study tested whether the marrow-suppressive activity of LGLs obtained at the time of marrow graft rejection was major histocompatibility complex ( MHC)-restricted. Five dogs were in the process of rejecting their DLA- nonidentical unrelated marrow grafts after conditioning with 9.2 Gy to tal-body irradiation (TBI). At the time of rejection, peripheral blood mononuclear cells (PBMC) were harvested. PBMC were co-cultured with m arrow obtained from the original marrow transplant donor and from othe r unrelated dogs that were either DLA-identical or -nonidentical with the marrow donor. A statistically significant reduction of marrow dono r CFU-GM was seen when compared to results with autologous effector PB MC from the marrow donor. The number of colonies with recipient effect or PBMC ranged from 8 to 75% (median 29%). No suppression was seen wit h PBMC effecters from unrelated DLA-identical or DLA-nonidentical dogs . Similarly, significant reductions in the number of CFU-GM compared t o autologous controls were seen with effector PBMC from marrow recipie nts and marrow target cells, both from unrelated dogs that were phenot ypically DLA-identical or -nonidentical with the marrow donor. The num ber of colonies ranged from 6 to 68% (median 29%) and 1 to 102% (media n 20%), respectively. NK activity was present at low levels in all rec ipients, while specific alloantigen-primed cytotoxic T cell killing by cells obtained from the five recipients yielded cytolysis of donor PB MC in only one case, suggesting that the marrow-suppressive activity w as NK cell-mediated. In conclusion, PBMC from canine marrow transplant recipients undergoing rejection of DLA-nonidentical marrow grafts sup press in vitro CFU-GM growth of marrow donor cells, and this suppressi on is not MHC-restricted.