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.

Preoperative Aqueous Cytokine Levels are Associated With Endothelial Cell Loss After Descemet's Stripping Automated Endothelial Keratoplasty

“…20,45 Richer et al 44 reported strong correlations between sICAM-1 and soluble apoptotic factors, such as soluble Fas and Fas ligand in rhegmatogenous retinal detachment. Recently, Dohlman et al 46 found that blockade of Eselectin suppressed graft rejection in murine corneal transplantation model, whereas both levels of E-selectin and Pselectin were upregulated in the rejected graft. Although there were no eyes with graft rejection after DSAEK in the case series, future studies on the immunologic mechanism of ECD loss after DSAEK will be valuable.…”

Kinetics of Angiogenic Responses in Corneal Transplantation

“…16–22 This is due to lymphatic and blood vessels acting as mediators of the afferent and efferent arms of the immune system, respectively, whereby lymphatics mediate the trafficking of alloantigen and immune cells from the graft to lymphoid tissues, and blood vessels facilitate the homing of immune cells to the graft. 23–26 In the current study, we characterize the kinetics of vessel formation in the cornea in a mouse model of corneal transplantation in order to determine how the kinetics of neo-hemangiogenesis and neo-lymphangiogenesis differ in the two distinct settings: (i) low-risk recipients that have no pre-existing corneal blood and lymphatic vessels, and (ii) high-risk recipients whose corneas have ample blood and lymphatic vessels prior to transplantation. 27 …”

Elevated Cytokine Levels in the Aqueous Humor of Eyes With Bullous Keratopathy and Low Endothelial Cell Density

“…These molecules play important parts in the other diseases, such as asthma, 44 atopic dermatitis, 45 and coronary artery disease. 46,47 Recently, Dohlman et al 48 reported that E-selectin, not P-selectin, mediates the trafficking of immune cells in graft rejection after murine corneal transplantation. The current study is the first report on Eselectin, P-selectin, and sICAM-1 in human AqH.…”