The “Unusual Suspects” in Allograft Rejection: Will T Regulatory Cell Therapy Arrest Them?

Abstract

Several trials with adoptively transferred T regulatory cells (TRegs) have shown to be safe and—in some instances—to be effective in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation (to prevent graft-versus-host disease), with type 1 diabetes (to preserve residual beta cell function), and with refractory Crohn’s disease (to control the disease). In solid organ transplantation, TReg-cell therapy trials with TReg-supportive immunosuppression are currently being undertaken to control the well-documented T effector cells responsible for allograft rejection. Emerging reports show that many “unusual suspects” are involved in allograft rejection as well. Whether TReg-cell therapy will also target them remains to be investigated. In this review, we will shed some light on these underscored cells, the role TRegs would potentially have in controlling these unusual suspects, and the immune-monitoring strategies that would address potential TReg-cell therapy efficacy.