Recipient-specific donor cytotoxic T lymphocytes enhance engraftment of unrelated, DLA non-identical canine marrow.
Resistance to canine marrow grafts from unrelated DLA non-identical donors can be overcome by infusion of viable donor peripheral blood leukocytes or thoracic duct cells in addition to the marrow. The mechanisms by which these cells enhance engraftment are unknown but are likely to include a graft-versus-host reaction. The current study investigated whether recipient-specific, donor alloreactive cytotoxic lymphocytes mediating a graft-versus-host reaction could abrogate resistance to canine marrow grafts. To this purpose, cytotoxic donor lymphocytes (CTL) specific for recipient DLA antigens were generated in vitro and expanded in culture by exogenous interleukin-2 (IL-2). Two groups of dogs were studied. All were given 9.2 Gy total body irradiation followed by 3.7 x 10(8) marrow cells/kg from an unrelated DLA non-identical donor on day 0 and 1.2 x 10(8) host-specific CTL/kg on days 1 and 2. Dogs in group 2 were given, in addition, subcutaneous injections of recombinant human IL-2, 10,000 U/kg twice daily on days 1 through 10 post-grafting. Ten of 16 dogs in the two groups showed hematopoietic engraftment regardless of whether they received in vivo IL-2. Engraftment in current dogs was significantly better than that in 47 controls given marrow alone (p = 0.001), although it was worse than that in 64 dogs given marrow and an order of magnitude higher number of viable mononuclear cells obtained from the peripheral blood (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)
Schwarzinger
I
I
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Raff
R F
RF
Flowers
M
M
Niederwieser
D
D
Graham
T
T
Shulman
H
H
Appelbaum
F R
FR
Schuening
F
F
Storb
R
R
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D006087:Graft vs Host Reaction / Q000276:immunology; D006648:Histocompatibility / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000032:analysis / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D014019:Tissue Donors; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D011994:Recombinant Proteins; C039692:histocompatibility antigen DLA