NATURAL-KILLER-CELLS AS EFFECTOR-CELLS OF GRAFT-VERSUS-LEUKEMIA ACTIVITY IN A MURINE TRANSPLANTATION MODEL

The transfer of cytotoxic effector cells reduces the risk of relapse a fter allogeneic BMT. Two murine leukemia cell lines, A20 (B lymphocyti c) and WEHI-3 (myelomonocytic), were used to investigate antileukemic effector mechanisms operating independently from graft-versus-host dis ease (GVHD). Different results were obtained with the two leukemia mod els. After injection of A20 cells, the majority of Balb/c recipients t reated with syngeneic BMT died due to leukemia relapse (89%). The tran splantation of MHC-matched DBA marrow resulted in chronic GvHD but did not reduce the risk of relapse (86%). Grafting of MHC-mismatched (but GvH-nonreactive) marrow cells from (C57xBalb)F1 hybrids, however, led to a significantly lower relapse rate (47%, p < 0.05). In vitro testi ng revealed that F1 cells but not Balb/c or DBA cells exert NK cell ac tivity against A20. The elimination of NK 1.1-positive cells from the graft reduced the antileukemic activity of (C57xBalb)F1 marrow against A20 in vivo. After injection of WEHI-3 leukemia cells, syngeneic BMT cured most of the recipients (62%) and transplantation of (C57xBalb)F1 marrow provided no additional benefit. In contrast to unmanipulated B alb/c and (C57xBalb)F1 cells, which showed no NK activity against WEHI -3 in vitro, IL-2 treated effector cells were highly cytotoxic. Transf er of IL-2 preincubated grafts significantly decreased the relapse rat e of WEHI-3 (19 vs. 38%) after syngeneic and allogeneic BMT. Our data indicate that GvL activity can be separated from GvHD. In our murine m odel, GvL activity appears to depend more on the donors NK/LAK cell ac tivity than on the presence or absence of GvHD.