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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Sydney X LuMarcel R M van den Brink

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 ...Continue Reading

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Citations

May 12, 2012·Nature Reviews. Immunology·Bruce R BlazarMehrdad Abedi
Mar 8, 2016·The Journal of Clinical Investigation·Hung D NguyenXue-Zhong Yu
Jan 18, 2017·Blood·Katarina RiesnerOlaf Penack
Jan 3, 2013·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·N M ValenzuelaE F Reed
Apr 16, 2015·Liver International : Official Journal of the International Association for the Study of the Liver·Haibo SunJunqi Niu
Feb 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eric PerkeyIvan Maillard
Dec 17, 2020·Frontiers in Immunology·Mahinbanu MammadliMobin Karimi
Apr 15, 2021·IScience·Mahinbanu MammadliMobin Karimi
Apr 27, 2021·Frontiers in Immunology·Mahasweta Gooptu, Joseph Harry Antin

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