title: Donor natural killer (NK1.1+) cells do not play a role in the suppression of GVHD or in the mediation of GVL reactions after DLI.
abstract: Donor regulatory T cells (CD3+ alphabetaT-cell receptor [TCR]+) derived from the repopulating host thymus have been shown to be primarily responsible for suppression of GVHD following DLI therapy in murine BMT models. However, natural killer (NK) T cells also have regulatory properties, and a role for NK T cells in suppression of GVH reactivity has not been completely excluded. NK cells may also contribute to the graft-versus-leukemia (GVL) effect associated with DLI therapy. In this study, we used a murine BMT model (C57BL/6 into AKR) to study whether depletion of donor NK cells had any impact on the suppression of GVH reactivity after DLI or on the DLI-induced GVL effect against acute T-cell leukemia. Depletion of donor NK cells was accomplished in vivo by giving DLI-treated bone marrow chimeras multiple injections of anti-NK1.1 monoclonal antibody (MoAb). The chimeras treated with anti-NK1.1 MoAb had significantly fewer splenic NK1.1 cells than nontreated chimeras, and splenocytes from anti-NK1.1-treated mice were deficient in the ability to generate lymphokine-activated lytic activity. Results presented here showed that NK-cell depletion had no effect on the suppression of GVH reactivity after DLI. When DLI-treated chimeras were challenged with an acute T-cell leukemia, NK-cell depletion had no discernible effect on GVL reactivity. These preclinical data suggest that donor NK cells do not have a significant role in the suppression of GVHD after DLI or in the mediation of GVL reactivity induced by DLI.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. bjohnson@mcw.edu
authors.forename: B D
authors.initials: BD
authors.lastname: Johnson
authors.forename: N
authors.initials: N
authors.lastname: Dagher
authors.forename: W C
authors.initials: WC
authors.lastname: Stankowski
authors.forename: C A
authors.initials: CA
authors.lastname: Hanke
authors.forename: R L
authors.initials: RL
authors.lastname: Truitt
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016026:Bone Marrow Transplantation / Q000379:methods / Q000401:mortality; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D007942:Leukemia, Experimental / Q000628:therapy; D017708:Leukocyte Transfusion; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D015996:Survival Rate; D013997:Time Factors; D018183:Transplantation Chimera
chemical_list: D000911:Antibodies, Monoclonal