E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation

Abstract

Background Immune rejection continues to threaten all tissue transplants. Here we sought to determine whether P- and E- selectin mediate T cell recruitment in corneal transplantation and whether their blockade can reduce T cell graft infiltration and improve long-term corneal allograft survival. Methods In a murine model of allogeneic corneal transplantation, we used PCR and immunohistochemistry to investigate expression of P- and E-selectin in rejected versus accepted allografts, and lymph node flow cytometry to assess expression of selectin ligands by effector T cells. Using P- and E-selectin neutralizing antibodies we evaluated the effect of blockade on CD4 T cell recruitment, as well as the effect of anti-E selectin on long-term allograft survival. Results P- (93.3 fold, p<0.05) and E-selectin (17.1 fold, p<0.005) are upregulated in rejected versus accepted allogeneic transplants. T helper (Th)1 cells from hosts with accepted and rejected grafts express high levels of P-selectin glycoprotein ligand 1 and glycosylated CD43. In vivo blockade of P (0.47±0.03, p<0.05) and E selectin (0.49±0.1, p<0.05) reduced the number of recruited T cells compared to IgG control (0.98±0.1). Anti-E-selectin reduced the number of mature antigen-presenting cells trafficking to lymphoid tissue compared to control (6.96±0.9 vs. 12.67±0.5 p<0.05). Anti-E-selectin treatment delayed graft rejection and increased survival compared to control, although this difference did not reach statistical significance. Conclusions In a model of corneal transplantation, P- and E-selectin mediate T cell recruitment to the graft, E-selectin mediates APC trafficking to lymphoid tissue and blockade of E-selectin has a modest effect on improving long-term graft survival.