PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation

Transpl Int. 2008 Nov;21(11):1015-28. doi: 10.1111/j.1432-2277.2008.00726.x. Epub 2008 Jul 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antigen-Presenting Cells / immunology*
  • Antigens, CD / immunology
  • Antigens, CD / physiology*
  • Apoptosis Regulatory Proteins / physiology*
  • B7 Antigens
  • B7-1 Antigen / immunology
  • B7-H1 Antigen
  • Graft Rejection / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology
  • Mice
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic / immunology
  • Receptors, Tumor Necrosis Factor, Member 14 / immunology
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation Immunology / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7 Antigens
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • CD276 protein, human
  • Cd276 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Pdcd1lg2 protein, mouse
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • Receptors, Immunologic
  • Receptors, Tumor Necrosis Factor, Member 14
  • TNFRSF14 protein, human