Tim-3/Gal-9 Pathway Is Necessary for Corneal Allograft Survival

Abstract

Purpose: : T cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule of T cell function. Galectin (Gal)-9 is a Tim-3 ligand. The purpose of the present study was to determine the role of Tim-3/Gal-9 pathway in immune privilege of corneal allografts.

Methods: : We performed corneal allograft transplantation using C57BL/6 donors and BALB/c recipients. An alloantigen specific anterior chamber associated immune deviation (ACAID) model in mice was also used. These mice were administrated with anti-Tim-3 monoclonal antibodies (mAb), anti-Gal-9 mAb, or control rat IgG intraperitoneally. Graft survival and induction of ACAID were assessed. Expressions of Tim-3 and Gal-9 in secondary lymphoid organs in normal adult mice and in the recipients of corneal allograft were examined by flowcytometry.

Results: : Allograft survival in the recipients treated with anti-Tim-3 mAb or anti-Gal-9 mAb were significantly shorter than that in the control recipients. Gal-9 was expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and the eyes bearing the surviving allografts. Tim-3 expression was found on CD4-positive T cells in the posterior surface of surviving allografts. ACAID was induced in the recipients treated with anti-Tim-3 mAb or anti-Gal-9 mAb. Gal-9 expression was down regulated in lymph nodes of the recipients bearing rejected allografts, but Tim-3 expression was not changed in these recipients.

Conclusions: : Tim-3/Gal-9 pathway plays an immunosuppressive role in corneal allografts, but is not associated with induction of ACAID. Gal-9 expressed on corneal endothelium and Tim-3 expressing CD4+T cells infiltrating in the corneal grafts may play a role on the allograft survival within the cornea.

Keywords: immune tolerance/privilege • transplantation • ACAID