Tregs: The Sertoli cell’s secret weapon in transplant survival

Abstract

Abstract Advanced germ cells develop after central tolerance is established and express non-self antigen but are not destroyed by the immune system. They owe their survival in part to the physical and immunological barrier created by Sertoli cells (SC). The protective nature of SC has sparked interest in the field of transplant immunology as a way to prevent transplant rejection. Indeed, SC prolong the survival of various co-transplanted tissues. However, exactly how SC achieve this protection remains largely unexplored, as does their effectiveness in female recipients. Data from transplantation studies indicates that T regulatory cells (Tregs) are critical in graft survival. This study aims to determine if SC survive at comparable rates in males and females, and if SC survival is dependent on Tregs. Therefore, we transplanted SC from B6 mice into allogeneic BALB/c male and female immunosuppressive drugs. At day 20, all SC grafts survived in male recipients and at least 67% survived in female recipients. In both males and females, Tregs were detected in high numbers in surviving grafts. To further explore their role in SC graft survival, Tregs were depleted in male graft recipients. Analysis of SC grafts at day 20 showed that 57% of SC grafts survived and saw a return of Tregs, as detected through flow cytometry. Tregs remained depleted in the rejected grafts. Together, this data indicates that Tregs must be present for SC grafts to survive and that SC themselves may induce Tregs. To conclude, SC survive allotransplantation in males and females, possibly through the activation of Tregs. Supported by CH Foundation, NIAID