TY - JOUR
T1 - Absence of P-selectin in recipients of allogeneic bone marrow transplantation ameliorates experimental graft-versus-host disease
AU - Lu, Sydney X.
AU - Holland, Amanda M.
AU - Na, Il Kang
AU - Terwey, Theis H.
AU - Alpdogan, Onder
AU - Bautista, Jhoanne L.
AU - Smith, Odette M.
AU - Suh, David
AU - King, Christopher
AU - Kochman, Adam
AU - Hubbard, Vanessa M.
AU - Rao, Uttam K.
AU - Yim, Nury
AU - Liu, Chen
AU - Laga, Alvaro C.
AU - Murphy, George
AU - Jenq, Robert R.
AU - Zakrzewski, Johannes L.
AU - Penack, Olaf
AU - Dykstra, Lindsay
AU - Bampoe, Kevin
AU - Perez, Lia
AU - Furie, Bruce
AU - Furie, Barbara
AU - Van Den Brink, Marcel R.M.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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 in-filtration 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.
AB - 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 in-filtration 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.
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U2 - 10.4049/jimmunol.0903148
DO - 10.4049/jimmunol.0903148
M3 - Article
C2 - 20622117
AN - SCOPUS:77956402670
SN - 0022-1767
VL - 185
SP - 1912
EP - 1919
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -