IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation

We recently showed that IL-11 prevents lethal graft-versus-host disease (GV HD) in a murine bone marrow transplantation (BMT) model of GVHD directed ag ainst MHC and minor antigens. In this study, we have investigated whether I L-11. can maintain a graft-versus-leukemia (GVL) effect. Lethally irradiate d B6D2F1 mice were transplanted with either T cell-depleted (TCD) bone marr ow (BM) alone or with BM and splenic T cells from allogeneic BG donors. Ani mals also received host-type P815 mastocytoma cells at the time of BMT. Rec ipients were injected subcutaneously with recombinant human IL-11 or contro l diluent twice daily, from 2 days before BMT to 7 days after BMT TCD recip ients all died from leukemia by day 23. All control- and IL-11 treated allo geneic animals effectively rejected their leukemia, but IL-11 also reduced GVHD-related mortality. Examination of the cellular mechanisms of GVL and G VHD in this system showed that IL-11 selectively inhibited CD4-mediated GVH D, while retaining both CD4- and CD8-mediated GVL. In addition, IL-11 treat ment did not affect cyolytic effector functions of T cells after BMT either in vivo or in vitro. Studies with perforin-deficient donor T cells demonst rated that the GVL effect was perforin dependent. These data demonstrated t hat IL-11 can significantly reduce CD4-dependent GVHD without impairing cyt olytic function or subsequent GVL activity of CD8(+) T cells. Brief treatme nt with IL-11 shortly after BMT may therefore represent a novel strategy fo r separating GVHD and GVL.