Seeking the Sertoli cell complement inhibitory signature to prolong transplant survival

Abstract

Abstract Clinical transplantation can treat various illnesses, although without the use of toxic immunosuppressants transplanted tissue is rejected by the immune system. Complement, an enzymatic cascade that leads to cytolysis by insertion of the membrane attack complex (MAC), is a significant component in transplant rejection. Interestingly, Sertoli cells (SC) survive long-term after transplantation across immune barriers without immunosuppression. This study used allotransplant (between same species) and xenotransplant (between different species) models to investigate the role of complement inhibition in SC extended survival. Since SC were resistant to in vitro complement killing, mouse or pig SC were transplanted into mice or rats, respectively. Grafts were collected and analyzed for MAC. MAC was not detected on SC transplants, indicating that SC inhibit complement before MAC deposition, possibly through expression of complement inhibitory proteins (CIP). Bioinformatic analyses of mouse or pig SC identified expression of 13 CIP. After expression of two key CIP, CD46 and CD55, were knocked down, SC were killed by complement in vitro. Taken together, these data indicate that the SC complement inhibitory signature is critical for SC graft survival. Understanding SC complement inhibition is important as it could lead to improved transplant survival with a decreased requirement of harsh immunosuppressants, making this procedure more attainable for patients. Supported by grants from the CH foundation, the South Plains Foundation, and the Mary Lou Clements-Mann Scholarship