Sirolimus-based regimen promotes inhibitory costimulatory signal of HVEM/BTLA/CD160/LIGHT pathway in allo-renal recipients

Abstract

HVEM/BTLA/CD160/LIGHT pathway is a very special costimulatory molecule system which can regulate T-cell immune responses by activating both inflammatory and inhibitory signalings. The regulatory effect of Sirolimus on HVME costimulatory system in allo-renal recipients has not been reported. In this study, we analyzed the expression of HVEM, BTLA, CD160 and LIGHT on circulating T cell subgroups and the expression of HVEM on CD4+ Tregs by flow cytometry and also the pre-dose concentration of Sirolimus by automatic analyzer. Both the allo-renal recipients receiving Sirolimus immunosuppressive regimen and health volunteers were included. The expression of both BTLA and CD160 on T cells increased significantly while the expression of LIGHT on T cells decreased significantly in allo-renal recipients receiving Sirolimus regimen (p<0.05). The expression of HVEM on T cells and CD4+ T-cell subgroup decreased (p<0.05) while that on CD8+ T-cell subgroup remained roughly normal (p>0.05).The expression of HVEM on CD4+ Tregs increased significantly (p<0.05) in allo-renal recipients receiving Sirolimus regimen (p<0.05). Though regulating the expression of HVEM/BTLA/CD160/LIGHT costimulatory system, Sirolimus-based regimen promotes inhibitory costimulatory signal in T cells and enhances the function of CD4+ Tregs in allo-renal recipients, which are in benefit of the control of transplant rejection as well as the induction and maintenance of transplant tolerance.