Graft-versus-host-disease (GVHD) is a systemic inflammatory disease that specifically affects the gastrointestinal tract, liver and skin. Modulating donor alloreactive T cell trafficking to these organs has been efficacious in ameliorating experimental GVHD. We demonstrate that P-selectin, a glycoprotein expressed on resting and inflamed endothelium, and a receptor for P-selectin-glycoprotein-ligand-1 (PSGL1), is important for the trafficking of donor alloactivated T cells into GVHD target organs. Compared with wildtype recipients of allogeneic bone marrow transplantation (allo-BMT), P selectin-/- recipients exhibit decreased GVHD mortality and decreased GVHD of the liver and small bowels. This was associated with diminished infiltration of alloactivated T cells into the Peyer's Patches and small bowels, coupled with increased numbers of donor T cells in the spleen and secondary lymphoid organs (SLO). This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO. We conclude that P selectin may be a viable target for GVHD prophylaxis or treatment.
