Effect of systemic anti-154 (CD40L) antibody on clinical outcomes of full-thickness porcine corneal graft in pig-to-rhesus corneal transplantation model (TRAN3P.872)

Abstract

Abstract Purpose: To investigate the effect of systemically administered anti-CD154 antibody(Ab) on the survival of full-thickness porcine corneal grafts. Methods: Seven rhesus macaques were assigned to control (n=3) or immunosuppression (n=4) group and underwent full-thickness corneal transplantation. Systemic steroid was applied to control group while anti-CD154 Ab were administered to immunosuppression group. Rejection sign, central corneal thickness (CCT), and recipients’ immunologic profile including memory T cell, anti-α-Gal and donor-specific Abs, mixed lymphocyte-like reaction and aqueous complement concentration were evaluated. Cellular infiltration into the xenografts was evaluated by immunohistochemical staining. Results: Anti-CD154 Ab-based immunosuppression significantly prolonged the survival of full-thickness xenocorneal grafts. In control group, CCTs, memory T cells, anti-α-Gal IgG and donor pig-specific IgG Abs continuously increased in correspond with the progression of graft rejection in contrast to immunosuppression group. Reactivities to donor-specific stimulators and concentrations of the aqueous complement were also significantly higher in control group than in immunosuppression group. Rejected grafts showed extensive cellular infiltration. Conclusions: Anti-CD154 antibody-based immunosuppression is effective for prolonging the survival of full-thickness xenocorneal grafts and controlling immunologic responses in pig-to-rhesus corneal transplantation model.