GITR Blockade Facilitates Treg Mediated Allograft Survival

Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade

CD40-CD40L blockade has potent immunosuppressive effects in cardiac allograft rejection but is less effective in the presence of inflammatory signals. To better understand the factors that mediate CD40-CD40L blockade-resistant rejection, we studied the effects of stimulation through glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by regulatory and effector ...

Endoplasmic Reticulum Stress-Mediated Apoptosis Involved in Indirect Recognition Pathway Blockade Induces Long-Term Heart Allograft Survival

Implementation of dendritic cell- (DC-) based therapies in organ transplantation can reduce dependency on nonspecific immunosuppression. Despite extensive research, mechanisms of equipped DCs inducing transplant tolerance remain incomplete. Here, we applied RNA interference technique to inhibit CD80 and CD86 expression in host bone marrow-derived DCs. This approach could specifically and effect...

Routes to allograft survival.

Caspase Inhibitor Therapy Synergizes With Costimulation Blockade to Promote Indefinite Islet Allograft Survival

OBJECTIVE Costimulation blockade has emerged as a selective nontoxic maintenance therapy in transplantation. However, these drugs must be combined with other immunomodulatory agents to ensure long-term graft survival. RESEARCH DESIGN AND METHODS Recent work has demonstrated that caspase inhibitor therapy (EP1013) prevents engraftment phase islet loss and markedly reduces the islet mass requir...

No synergy between ATG induction and costimulation blockade induced kidney allograft survival in rhesus monkeys.

BACKGROUND Costimulation blockade with antibodies directed against human CD40 and CD86 leads to prolonged kidney allograft survival in rhesus monkeys, but fails to induce permanent graft acceptance. We have tested whether costimulation blockade is more effective after peripheral T-cell ablation with antithymocyte globulin (ATG), with the aim to remove already primed autoreactive cells present i...