title: 'Resistance' to unrelated, DLA-nonidentical canine marrow grafts is unrestricted by the major histocompatibility complex.
abstract: Dogs undergoing rejection of unrelated, dog leukocyte antigen (DLA)-nonidentical marrow grafts show an increase in mononuclear cell counts in the peripheral blood at 1 week after transplant. Cells are of host origin and express phenotypic and morphologic characteristics of large granular lymphocytes (LGLs). LGLs from rejecting dogs suppress in vitro 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 total-body irradiation (TBI). At the time of rejection, peripheral blood mononuclear cells (PBMC) were harvested. PBMC were co-cultured with marrow obtained from the original marrow transplant donor and from other unrelated dogs that were either DLA-identical or -nonidentical with the marrow donor. A statistically significant reduction of marrow donor CFU-GM was seen when compared to results with autologous effector PBMC from the marrow donor. The number of colonies with recipient effector PBMC ranged from 8 to 75% (median 29%). No suppression was seen with PBMC effectors from unrelated DLA-identical or DLA-nonidentical dogs. Similarly, significant reductions in the number of CFU-GM compared to autologous controls were seen with effector PBMC from marrow recipients and marrow target cells, both from unrelated dogs that were phenotypically DLA-identical or -nonidentical with the marrow donor. The number of colonies ranged from 6 to 68% (median 29%) and 1 to 102% (median 20%), respectively. NK activity was present at low levels in all recipients, while specific alloantigen-primed cytotoxic T cell killing by cells obtained from the five recipients yielded cytolysis of donor PBMC in only one case, suggesting that the marrow-suppressive activity was NK cell-mediated. In conclusion, PBMC from canine marrow transplant recipients undergoing rejection of DLA-nonidentical marrow grafts suppress in vitro CFU-GM growth of marrow donor cells, and this suppression is not MHC-restricted.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092.
authors.forename: R F
authors.initials: RF
authors.lastname: Raff
authors.forename: B M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: T
authors.initials: T
authors.lastname: Graham
authors.forename: T P
authors.initials: TP
authors.lastname: Loughran
authors.forename: M
authors.initials: M
authors.lastname: Pettinger
authors.forename: R
authors.initials: R
authors.lastname: Storb
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002478:Cells, Cultured; D004285:Dogs; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006098:Granulocytes / Q000166:cytology; D006649:Histocompatibility Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000166:cytology; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D010641:Phenotype; D014019:Tissue Donors
chemical_list: D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA