Immunology in corneal transplantation—From homeostasis to graft rejection

Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs. Xenotransplantation, like using porcine corneas for human transplants, offers a potential solution to the donor tissue shortage but faces substantial immunological rejection issues. To prevent rejection in both allo- and xenotransplantation, a deep understanding of how the body maintains immunological balance is essential, particularly since achieving tolerance to non-self tissues is considered the “holy grail” of the field. The cornea, the most frequently transplanted solid organ, has a high acceptance rate due to its immune-privileged status and serves as an ideal model for studying graft rejection mechanisms that disrupt tolerance. However, multiple immune pathways complicate our understanding of these mechanisms. This review examines the rejection mechanisms in corneal transplantation, identifying key cells involved and potential therapeutic strategies to induce and maintain immunological tolerance in both allo- and xenografts across various transplants.