title: Facilitation of engraftment of DLA-nonidentical marrow by treatment of recipients with monoclonal antibody directed against marrow cells surviving radiation.
abstract: Past studies in dogs have suggested that marrow graft rejection was mediated by major histocompatibility complex (MHC) class II antigen-positive non-T cells that survived standard doses of total-body irradiation (TBI). We have now raised 4 monoclonal antibodies (mAbs) against marrow cells harvested 6 days after TBI. The mAbs are highly reactive (greater than 70%) with marrow cells surviving radiation and also bind strongly (greater than 50%) to normal marrow cells, lymphocytes, monocytes, and granulocytes. One of the mAbs (34-S3) reacted strongly with NK-like cells. In vitro treatment of marrow with mAb and rabbit complement (C') did not affect erythroid colony-forming unit (CFU-E) growth, whereas 2 of the 4 mAbs inhibited granulocyte-macrophage colony-forming unit (CFU-GM) growth, and all 3 mAbs tested suppressed autologous marrow engraftment. One of the mAbs, 69-S5 (IgG1), bound to a 95,000 dalton antigen. It crossreacted with human cells, but not with cells from Rhesus monkeys, baboons, and cats. We administered this mAb intravenously at 0.2 mg/kg/day on days -5 to 0 to dogs given 9.2 Gy TBI on day 0 followed by marrow grafts (less than or equal to 4 x 10(8) cells/kg) from DLA-nonidentical unrelated donors. Three of five dogs had sustained grafts. Increasing the dose of mAb ten-fold (2 mg/kg/day) resulted in graft failure (2 of 2 dogs). Treatment with a dose of 0.2 mg/kg/day from day -7 to -2 showed sustained engraftment in 7 of 10 dogs. This result is in contrast to sustained grafts in 3 of 36 dogs not given mAb, and in 1 of 7 dogs treated with an irrelevant mAb (P = 0.0002 and 0.04, respectively). We conclude that treatment of recipients with a mAb raised against marrow cells surviving radiation and not directed at major histocompatibility complex (MHC) class II antigens and NK-like cells can also facilitate engraftment of DLA-nonidentical canine marrow. These results may be relevant for the transplantation of HLA-incompatible marrow in man, particularly after in vivo T cell depletion, where graft failure is frequent.
authors.affiliation: Division of Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
authors.forename: F
authors.initials: F
authors.lastname: Schuening
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: S
authors.initials: S
authors.lastname: Goehle
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: T C
authors.initials: TC
authors.lastname: Graham
authors.forename: H J
authors.initials: HJ
authors.lastname: Deeg
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: G E
authors.initials: GE
authors.lastname: Sale
authors.forename: L
authors.initials: L
authors.lastname: Graf
authors.forename: T P
authors.initials: TP
authors.lastname: Loughran
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D003429:Cross Reactions; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D004912:Erythrocytes; D006098:Granulocytes; D006412:Hematopoietic Stem Cells; D006649:Histocompatibility Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages; D014916:Whole-Body Irradiation
chemical_list: D000911:Antibodies, Monoclonal; D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA