Evidence for a possible role of Asialo-GM1-positive cells in the graft-versus-leukemia repression of a murine type-C retroviral leukemia.
Studies were performed to examine whether, in addition to T cells, there might be other immune cells also capable of exerting a graft-versus-leukemia (GVL) response following allogeneic marrow transplant. Using an MHC-matched mouse model, consisting of normal B10.S donors and SJL/J Rauscher-retroviral-leukemic recipients, the donor cells were selectively depleted of their Asialo-GM1+ component prior to being infused into the leukemic recipients. The incidence of relapse was then compared against that for matched leukemic control recipients of undepleted cells from the same donors. FCM analysis of the depletion protocol indicated that exposure to anti-Asialo-GM1 antibody eliminated more than half of the donor NK1.1+ cells, but caused no significant losses among the Thy-1+, CD3+, or CD8+ cells. Nevertheless, fatal relapse among the leukemic recipients of the depleted cells was nearly double that found among the leukemic control recipients of undepleted cells, 47.5 vs 25.4% (P = 0.01). In a parallel study, using normal SJL/J recipients, this same depletion protocol was found to have no significant effect on the incidence of graft-versus-host disease (GVHD). These results therefore suggest that Asialo-GM1+ NK cells may be capable of contributing to the suppression of relapse in this type of leukemic recipient of allogeneic marrow, and that this suppression may occur independently of GVHD.
OKunewick
J P
JP
Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
Kociban
D L
DL
Machen
L L
LL
Buffo
M J
MJ
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D005677:G(M1) Ganglioside / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006086:Graft vs Host Disease; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology* / Q000601:surgery; D051379:Mice; D008815:Mice, Inbred Strains; D012008:Recurrence; D012190:Retroviridae
D000906:Antibodies; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside