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

Item Type:Article
Title:Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease
Creators Name:Lu, S.X. and Holland, A.M. and Na, I.K. and Terwey, T.H. and Alpdogan, O. and Bautista, J.L. and Smith, O.M. and Suh, D. and King, C. and Kochman, A. and Hubbard, V.M. and Rao, U.K. and Yim, N. and Liu, C. and Laga, A.C. and Murphy, G. and Jenq, R.R. and Zakrzewski, J.L. and Penack, O. and Dykstra, L. and Bampoe, K. and Perez, L. and Furie, B. and Furie, B. and van den Brink, M.R.M.
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.
Keywords:Animal Disease Models, Bone Marrow Transplantation, Graft vs Host Disease, Homologous Transplantation, Inflammation Mediators, Ligands, Lymphocyte Activation, Membrane Glycoproteins, P-Selectin, T-Lymphocyte Subsets, Vascular Endothelium, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:1912-1919
Date:1 August 2010
Official Publication:https://doi.org/10.4049/jimmunol.0903148
PubMed:View item in PubMed

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