Role of VEGFR-3 on Corneal Lymphatic Drainage, Antigen-Presenting Cell Trafficking and Alloimmunity

Abstract

Abstract: : Purpose: Previous data from our lab indicate that trafficking of antigen presenting cells (APC) to draining lymph nodes (LN) plays a critically important role in corneal immunity (Yamagami S. & Dana M.R., 2001; Liu Y., et al, 2002). VEGFR-3 (Flt-4) is a tyrosine kinase receptor which is mainly expressed on the lymphatic endothelium in adult tissues. Our preliminary data have shown its expression on the endothelium of lymphatic vessels in the limbus and conjunctiva, as well as on corneal APCs. The purpose of this study was to investigate the role of VEGFR-3 in APC trafficking after corneal transplantation. Methods: Orthotopic corneal transplantation was performed between C57BL/6 (Ia^b;donor) and BALB/c (Ia^d; recipient) mice. BALB/c mice were randomly selected to receive either varying doses of VEGFR-3/Ig chimeric molecule via subconjunctival injection (day 0) or vehicle control. 48h after grafting the ipsilateral draining LNs were collected and frozen sections were used for immunofluorescence staining for donor-derived MHC class II antigens (Ia^b). Results: Ia^b+ cells were detected in the draining LNs 48h after corneal transplantation and the number was inversely correlated with the dose of VEGFR-3/Ig administered. Conclusions: Corneal APC trafficking is greatly reduced by blocking the ligand-receptor interaction of VEGFR-3 by use of VEGFR-3/Ig. Additional studies targeting this receptor-ligand interaction are required to further define the possible functional role of this receptor in graft survival and induction of alloimmunity.

Keywords: transplantation • immunomodulation/immunoregulation • cornea: basic science