Control of peripheral T‐cell tolerance and autoimmunity via the CTLA‐4 and PD‐1 pathways

By B. Fife, J. Bluestone. Immunological Reviews, 2008

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Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T Cell Rejection Function in Tumors (2013, background): “Despite these similarities as terminators of T-cell activation, the difference in regulatory roles of the PD-1 and CTLA-4 pathways has been recognized (27-29).”
CTLA-4 and PD-1 Pathways (2016, background): “The B7 ligands for CTLA-4 are expressed by professional APCs, which typically reside in lymph nodes or spleen(2); however, PD-L1 and PD-L2 are more widely expressed.(2,10,23,24) PD-L1 is expressed on leukocytes, on nonhematopoietic cells, and in nonlymphoid tissues, and can be induced on parenchymal”
Interactions between programmed death-1 and programmed death ligand-1 promote tolerance by blocking the T cell receptor-induced stop signal (2009, background): “However, the effects of PD-1 engagement during T cell activation are unclear, as in vitro models have not adequately demonstrated the inhibitory activity of PD-1 (ref”
PD-1 signaling in primary T cells (2009, background): “We and many others have shown that the main targets of negative regulators of T-cell activation are cell growth and metabolism (13, 15, 39, 83).”