Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease
Authors
- S.X. Lu
- A.M. Holland
- I.K. Na
- T.H. Terwey
- O. Alpdogan
- J.L. Bautista
- O.M. Smith
- D. Suh
- C. King
- A. Kochman
- V.M. Hubbard
- U.K. Rao
- N. Yim
- C. Liu
- A.C. Laga
- G. Murphy
- R.R. Jenq
- J.L. Zakrzewski
- O. Penack
- L. Dykstra
- K. Bampoe
- L. Perez
- B. Furie
- B. Furie
- M.R.M. van den Brink
Journal
- Journal of Immunology
Citation
- J Immunol 185 (3): 1912-1919
Abstract
Alloreactive T cells are crucial for graft-versus-host disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report in this paper that P-selectin, a glycoprotein found on resting and inflamed endothelium, is important for donor alloreactive T cells trafficking into GVHD target organs, such as the intestines and skin. Compared with wild-type (WT) recipients of allogeneic bone marrow transplantation, P-selectin(-/-) recipients exhibit decreased GVHD mortality and decreased GVHD of the skin, 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 (SLOs). Surprisingly, however, donor T cells deficient for P-selectin glycoprotein ligand 1, the most well described P-selectin ligand, mediated GVHD similar to WT T cells and accumulated in SLO and target organs in similar numbers as WT T cells. This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO and that donor T cells may use multiple P-selectin ligands apart from P-selectin glycoprotein ligand 1 to interact with P-selectin and traffic into inflamed tissues during GVHD. We conclude that targeting P-selectin may be a viable strategy for GVHD prophylaxis or treatment.