Involvement of DNAM-1 in the development of graft-versus-host disease

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Graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation ; however, no effective molecular targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAM-1 had significantly lower mortality than those that received wild-type (WT) splenocytes. Donor CD8+T cells deficient in DNAM-1 showed less proliferation and produced less interferon-γ after coculture with allogeneic splenocytes than WT CD8+ T cells. Mice prophylactically treated with an anti-DNAM-1 antibody showed low mortality. Moreover, treatment with a single administration of the antibody after the onset of GVHD prolonged survival. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.