Abstract
Purpose: :
In recent studies, we showed that DAF and CD59, originally characterized as cell surface regulators which protect self cells from complement attack, play a central role in the induction of T cell response. In other work, we showed that the two molecules are essential for anterior chamber–associated immune deviation (ACAID). To study their importance in suppressing T cell responses against corneal transplants, we measured T cell anti–male Dby and Uty responses following transplantation of male corneas from Daf1–/–CD59a–/– mice or WTs to female WT recipients, and male corneas from Daf1–/–CD59a–/– mice or WTs to female Daf1–/–CD59a–/– recipients.
Methods: :
2 mm corneal grafts from each of the mouse groups were transplanted using 8 interrupted sutures into 1.5 mm beds. All animals were mixed 129/C57BL/6 backcrossed 5 generations on the C57BL/6 background. Following transplantation, rejection was graded clinically, histology analyzed, and recipient CD4 and CD8 responses to male antigen measured by IFN–γ ELISPOTS to Dby and Uty respectively.
Results: :
Marked responses to both CD4–restricted Dby and CD8–restricted Uty were seen in Daf1–/– transplants and Daf1–/–CD59a–/– corneas. Similarly increased results were found when WT male corneas were used and when recipients were deficient in DAF or both regulators.
Conclusions: :
DAF and CD59 on both transplants and recipients are necessary to suppress both CD4 and CD8 responses to corneal transplantation. The results suggest that administration of DAF and/or CD59 could have clinical value in high risk transplants.
Keywords: cornea: basic science • immunomodulation/immunoregulation • inflammation