Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease

J Immunol. 2010 Aug 1;185(3):1912-9. doi: 10.4049/jimmunol.0903148. Epub 2010 Jul 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Transplantation / immunology*
  • Disease Models, Animal
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / physiopathology
  • Graft vs Host Disease / therapy*
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Ligands
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • P-Selectin / genetics*
  • P-Selectin / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocyte Subsets / transplantation
  • Transplantation, Homologous


  • Inflammation Mediators
  • Ligands
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein