Prevention of graft-versus-host disease by anti-1L-7Rα antibody

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 anti body-mediated blockade of IL-7 receptor alpha (IL-7R alpha) signaling. C57/BL6 (H2K(b)) recipient mice were lethally irradiated and underwent cotransplantation with T-cell-depleted (TCD) ISM and lymph node (LN) cells from allogeneic BALB/c (H2K(d)) donor mice. Following transplantation, the allogeneic BMT recipients were injected weekly with either anti-IL-7R alpha antibody (100 mu g per mouse per week) or PBS for 4 weeks. Anti-IL-7R alpha. antibody treatment significantly decreased GVHD-related morbidity and mortality compared with placebo (30% to 80%). IL-7R alpha 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-7R alpha antibody treatment resulted in improved long-term thymic and immune function. Blockade of IL-7R by anti-IL-7R alpha antibody resulted in elimination of alloreactive T cells, prevention of GVHD, and improvement of donor T-cell reconstitution.