Abstract
Purpose: Corneal transplantation is the most frequently performed solid organ transplantation procedure worldwide. We aimed to investigate the role of extracellular vesicles in allorecognition and the rejection of allografts in corneal transplantation using male C57BL/6 (B6 and IAb) and BALB/c (IAd) mice. Methods: The mice were aged 8 to 12 weeks. We used transmission electron microscopy to visualize the drainage of extracellular vesicles derived from the graft into the cervical lymph nodes using gold colloids as markers in a mouse model of corneal transplantation. Results: Lymph node cells sensitized to graft-derived extracellular vesicles exhibited high proliferation when exposed to cultured corneal stromal cells in a mixed lymphocyte reaction. Notably, extracellular vesicles carrying graft-derived IA antigens were detected in cervical lymph nodes within a maximum of 6 hours postoperatively. Moreover, the administration of extracellular vesicles extracted from cultured corneal stromal cells significantly reduced the graft survival rate. Conclusions: These findings provide the first evidence of a semi-direct pathway in which graft-derived extracellular vesicles are captured in cervical lymph nodes and contribute to the promotion of allograft rejection in corneal transplantation.