Notch signaling in alloreactive T cell immunity

Alloreactive T cell immunity mediates the recognition of foreign tissue antigens in recipients of organ transplants. After solid organ transplantation, activation of host T cells by donor alloantigens can trigger rejection of the implanted organ. Global life-long immunosuppression is necessary to prevent or to minimize organ rejection. After bone marrow or hematopoietic cell transplantation (allo-BMT), donor-derived T cells recognize host alloantigens, inducing both beneficial graft-versus-tumor (GVT) effects as well as detrimental graft-versus-host disease (GVHD). Preventing GVHD without eliminating GVT activity is an essential goal to maximize the safety and efficacy of allo-BMT. In this review, we discuss emerging findings that have identified the Notch pathway as a central player in the regulation of T cell alloimmunity. In view of these effects, Notch signaling in T cells should be considered as an attractive new therapeutic target to achieve beneficial immunomodulation following allo-BMT and other types of allogeneic transplantation.