PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation.
Transplantation of cells, tissues and vascularized solid organs is a successful therapeutic intervention for many end-stage chronic diseases. The combination of co-stimulatory blockade with the delivery of negative signals to T cells through co-inhibitory receptors would provide a robust approach to modulating T-cell receptor signaling and improving alloantigen-specific control of transplant rejection. This approach based on fundamental knowledge of APC/T-cell interactions may complement conventional therapies in the near future to reinforce long-term allograft survival, and permit minimal immunosuppression. The focus of this review was primarily on two major co-inhibitory signaling pathways, namely PD-1/PD-L1/PD-L2 and BTLA/CD160/HVEM/LIGHT that have been thoroughly characterized in murine models of transplantation using genetically modified mice, specific monoclonal antibodies and fusion proteins.
del Rio
Maria-Luisa
ML
Laboratory of Immunobiology, School of Biotechnology and Institute of Biomedicine, University of Leon, Leon, Spain.
Buhler
Leo
L
Gibbons
Carrie
C
Tian
Jiong
J
Rodriguez-Barbosa
Jose-Ignacio
JI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000276:immunology; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060887:B7 Antigens; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C423237:CD276 protein, human; C486038:Cd276 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506028:TNFRSF14 protein, human