Abstract
Purpose :
The T cell/transmembrane, immunoglobulin, and mucin (TIM) gene family plays a critical role in regulating immune responses, including transplant tolerance, autoimmunity, the regulation of allergy and asthma, and the response to viral infections. The TIM gene family consists of three members (TIM-1, TIM-3, and TIM-4) on human chromosome. TIM molecules provide a functional repertoire for recognition of apoptotic cells, which determines whether apoptotic cell recognition leads to immune activation or tolerance. We have previously shown that TIM-3 plays an immune suppressive role via Galection-9 in corneal allografts. It has been known that TIM-4-expressing cells bounds and engulfed apoptotic cells, but its role in the eye has been never known. The purpose of the present study is to investigate expression of TIM-4 in normal cornea and corneal grafts.
Methods :
Normal corneas of C57BL/6 or BALB/c mice were transplanted orthotopically into the normal eyes of BALB/c mice and graft survival was assessed. Accepted allograft, rejected allografts, and syngeneic grafts –bearing eyes were removed at 3 to 5 weeks after corneal transplantation. Expression of TIM-4 in the graft-bearing eyes was evaluated immunohistochemically by confocal microscopy. Normal eyes were used as control.
Results :
In normal eyes, TIM-4 was expressed on corneal epithelial cells, but not on resident CD11b+ cell in stroma. The expression of TIM-4 on epithelial cells was retained in corneal allo- and syngeneic-grafts. TIM4+CD11b+, TIM4+CD11C+, and TIM4+CD4+ TIM4+CD8+ cells were present in corneal stroma of allo- and syngeneic-grafts. Nubmers of these TIM4+ infiltrating cells in rejected allograft were significantly larger than that of accepted allografts and syngeniec grafts.
Conclusions :
TIM-4 is expressed in normal corneal epithelium. TIM-4 expressing antigen presenting cells and T cells infiltrates into corneal grafts, and may have a role in immune response.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.