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.
Life Sciences Institute.
Jooho
J
Chung
Ivan
I
Maillard
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D020350:Graft vs Tumor Effect / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D016377:Organ Transplantation; D051880:Receptors, Notch / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous
D016207:Cytokines; D007166:Immunosuppressive Agents; D007519:Isoantigens; D051880:Receptors, Notch