Dohlman, Thomas H.Di Zazzo, AntonioOmoto, MasahiroHua, JingDing, JuliaHamrah, PedramChauhan, SunilDana, Reza2018-02-202016Dohlman, Thomas H., Antonio Di Zazzo, Masahiro Omoto, Jing Hua, Julia Ding, Pedram Hamrah, Sunil K. Chauhan, and Reza Dana. 2016. “E-Selectin Mediates Immune Cell Trafficking in Corneal Transplantation.” Transplantation 100 (4) (April): 772–780. doi:10.1097/tp.0000000000001107.0041-1337http://nrs.harvard.edu/urn-3:HUL.InstRepos:34854265Background 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.en-USJournal Article2017-06-1920162018-02-2010.1097/tp.0000000000001107