Comprehensive Review
Role of the PD-1 Pathway in the Immune Response

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Understanding immunoregulatory mechanisms is essential for the development of novel interventions to improve long-term allograft survival. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, have emerged as critical inhibitory signaling pathways that regulate T cell response and maintain peripheral tolerance. PD-1 signaling inhibits alloreactive T cell activation, and can promote induced regulatory T cell development. Furthermore, the upregulation of PD-L1 on nonhematopoietic cells of the allograft may actively participate in the inhibition of immune responses and provide tissue-specific protection. In murine transplant models, this pathway has been shown to be critical for the induction and maintenance of graft tolerance. In this review, we discuss the current knowledge of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential in transplantation.

Key words:

Alloimmunity
costimulation
PD-1
PD-L1
PD-L2
regulatory T cells
tolerance
transplantation

Abbreviations:

BCR
B cell receptor
CTLA-4
cytotoxic T lymphocyte-associated antigen 4
DC
dendritic cell
EAE
experimental autoimmune encephalomyelitis
MHC
major histocompatibility complex
mOVA
membrane-bound chicken OVA
NOD
nonobese diabetic
PD-1
Programmed cell death-1
PD-L1
Programmed cell death-1 ligand
TCR
T cell receptor
TLR
Toll-like receptor

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