Regulatory T Cell Therapy in Transplantation

Receiving a kidney transplant currently requires patients to commit to life-long immunosuppression therapy. The combination of immunosuppressive drugs currently taken by transplant recipients often does achieve the right degree of immunosuppression. While over-immunosuppression is associated with increased risks of infection and malignancies, under-immunosuppression leads to graft rejection, reduced graft function over time, and even graft loss. Moreover, many commonly used immunosuppressive drugs are ironically nephrotoxic. Therefore, a more precise and less toxic approach to controlling alloimmune response against grafts is needed. The immune system has its own built-in control to prevent the attacking of one's own healthy organs. An essential component of immune self-tolerance is regulatory T cells (Tregs). Tregs are a special lineage of cells dedicated to preventing unwanted immune response, dampening inflammation, and restoring immune homeostasis after immune activation. Research demonstrates that Tregs also control alloimmune responses and Tregs can be used therapeutically to induce transplantation tolerance in preclinical models. Treg cell therapy harnesses the natural ability of immune self-regulation and has the potential to achieve more robust and specific control of antigraft responses. Translating Treg cell therapy to the clinic began in the late 2000s with 7 phase 1 clinical trials in graft-versus-host disease, type 1 diabetes, and liver transplantation published by mid-2016. In this chapter, we summarize preclinical developments, translational efforts, and clinical implementation of Treg cell therapy in transplantation.