Proangiogenic Function of T Cells in Corneal Transplantation

Abstract

Background Corneal neovascularization increases the risk of T cell mediated allograft rejection. Here, we investigate whether T cells promote angiogenesis in transplantation. Methods Conventional effector T cells were collected from draining lymph nodes (DLNs) of allogeneic or syngeneic corneal transplanted BALB/c mice. T cells were either cocultured with vascular endothelial cells (VECs) to assess VEC proliferation or used in a Mixed Lymphocyte Reaction assay. mRNA expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein expression was determined by ELISA. Flow cytometry was used to analyze VEGF-R2 expression in corneal CD31+ cells, and VEGF-A and IFNγ expression in corneal CD4+ T cells. Results Allogeneic T cells from high-risk (HR) grafted mice induced more VEC proliferation than those from syngeneic transplant recipients (p=0.03). VEGF-A mRNA and protein expression were higher in T cells from DLNs (p=0.03 and p=0.04, respectively) and cornea (protein; p=0.04) of HR compared to low-risk (LR) grafted hosts. VEGF-A, VEGF-C and VEGF-R2 mRNA expression were increased in VECs when cocultured with T cells from HR transplants compared to LR transplants and naïve mice. In addition, IFNγ blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein expression, whereas blocking VEGF-A significantly reduced VEC proliferation (p=0.04). Conclusions Allogeneic T cells from corneal transplant hosts promote VEC proliferation, probably via VEGF-A signaling, while IFNγ shows an antiangiogenic effect. Our data suggest that T cells are critical mediators of angiogenesis in transplantation.

The purinergic receptor antagonist oxidized adenosine triphosphate suppresses immune-mediated corneal allograft rejection

“…Results shown are representative of three independent experiments. Samples sizes were estimated based on previous experimental studies on corneal transplantation 29,30,39,45,46 .…”

Exploring the Key Genes and Pathways in the Formation of Corneal Scar Using Bioinformatics Analysis

“…e role of vascular endothelial growth factor in corneal neovascularization has been con rmed. e inhibitory e ect of vascular endothelial growth factor is currently being studied as a treatment for corneal neovascularization [30,31]. KEGG pathways in module 2 were mainly involved showed that Upregulated DEGs mainly participated in cell component (CC), while down regulated DEGs mainly took part in both cell component (CC) and molecular function (MF).…”

Mast cells contribute to the induction of ocular mucosal alloimmunity

“…[13][14][15] In this model of ocular alloimmunity, approximately half of the grafts are rejected within 3 weeks of transplantation, while the remaining half survive indefinitely. [13][14][15] In this model of ocular alloimmunity, approximately half of the grafts are rejected within 3 weeks of transplantation, while the remaining half survive indefinitely.…”

“…We investigated the function of mast cells using a well-characterized murine model of corneal transplantation. [13][14][15] In this model of ocular alloimmunity, approximately half of the grafts are rejected within 3 weeks of transplantation, while the remaining half survive indefinitely. In comparison with other transplant models, this system permits the continuous evaluation of the alloimmune response (through the assessment of graft opacity) without necessitating host sacrifice.…”