Prevention of graft-versus-host disease by anti–IL-7Rα antibody

Abstract

Abstract Graft-versus-host disease (GVHD) continues to be a serious complication that limits the success of allogeneic bone marrow transplantation (BMT). Using IL-7–deficient murine models, we have previously shown that IL-7 is necessary for the pathogenesis of GVHD. In the present study, we determined whether GVHD could be prevented by antibody-mediated blockade of IL-7 receptor α (IL-7Rα) signaling. C57/BL6 (H2Kb) recipient mice were lethally irradiated and underwent cotransplantation with T-cell–depleted (TCD) BM and lymph node (LN) cells from allogeneic BALB/c (H2Kd) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti–IL-7Rα antibody (100 μg per mouse per week) or PBS for 4 weeks. Anti–IL-7Rα antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7Rα blockade resulted in the reduction of donor CD4+ or CD8+ T cells in the periphery by day 30 after transplantation. Paradoxically, the inhibition of GVHD by anti–IL-7Rα antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti–IL-7Rα antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.