The DOI matches its Crossref record; 95 of the 95 references it cites were found in a registry or an index.
PD-1 signaling in primary T cells
Open accessAbstract
Summary: Programmed death‐1 (PD‐1) is a cell surface molecule that regulates the adaptive immune response. Engagement of PD‐1 by its ligands PD‐L1 or PD‐L2 transduces a signal that inhibits T‐cell proliferation, cytokine production, and cytolytic function. While a great deal is known concerning the biologic roles PD‐1 plays in regulating the primary immune response and in T‐cell exhaustion, comparatively little is known regarding how PD‐1 ligation alters signaling pathways. PD‐1 ligation is known to inhibit membrane‐proximal T‐cell signaling events, while ligation of the related inhibitory molecule cytotoxic T‐lymphocyte antigen‐4 appears to target more downstream signaling pathways. A major obstacle to an in‐depth understanding of PD‐1 signaling is the lack of physiologic models in which to study signal transduction. This review focuses on: (i) signaling pathways altered by PD‐1 ligation, (ii) factors recruited upon PD‐1 phosphorylation, and (iii) exploring the hypothesis that PD‐1 ligation induces distinct signals during various stages of immune‐cell differentiation. Lastly, we describe models to dissect the function of the PD‐1 cytoplasmic tail using primary cells in the absence of agonist antibodies.
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“it is suggested that recruitment of SH2-domain containing protein tyrosine phosphatases (SHP-1 and/or SHP-2) to the immunoreceptor tyrosine-based switch motif (ITSM) within the PD-1 cytoplasmic tail inhibits signaling events, particularly PI3K/AKT activation, downstream signals of the T-cell receptor [34], and in turn results in T cell dysfunction.”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [34]
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Cites
PD-1 and Its Ligands in Tolerance and Immunity
Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057 · cited 3×
“However, the striking overexpression of PD-1 on resting exhausted T cells and the restoration of immune function in exhausted T cells upon PD-1 blockade (5) forever changed PD-1’s perception as the easy child of the CD28 family.”
BackgroundInfluentialIshida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259 · cited 2×
“PD-1 was initially described as a molecule preferentially expressed in dying cells (1).”
BackgroundPD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955 · cited 1×
“Others have found that containing tyrosine phosphatase (SHP)-2 is recruited to the PD-1 cytoplasmic tail in a B-cell line (46) and in Jurkat T cells (47).”
BackgroundPD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Day, C. L., Kaufmann, D. E., Kiepiela, P., Brown, J. A., Moodley, E. S., Reddy, S., Mackey, E. W., Miller, J. D., Leslie, A. J., DePierres, C., et al. (2006) · Nature · doi:10.1038/nature05115 · Cited by 2,680
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496 · cited 1×
“Despite a few reports claiming its ligand PD-L1 (B7-H1) was a costimulatory molecule (93), the initial studies involving PD-1 function and signaling were relatively straightforward, especially when compared with the other members of the CD28 family (7).”
BackgroundGreenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318 · cited 1×
“SHP-2 is ubiquitously expressed and SHP-2 deficiency is embryonic lethal in mice (24).”
BackgroundMolecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103 · cited 2×
“Infection of mice with LCMV Armstrong or its closely related variant LCMV clone 13 initially generate similar LCMV-specific primary immune responses (4).”
BackgroundSiglecs and their roles in the immune system
Crocker, P. R., Paulson, J. C., & Varki, A. P. (2007) · Nature reviews. Immunology · doi:10.1038/nri2056 · Cited by 2,032 · cited 1×
“Members of the CD33-Siglec family are expressed on the surface of the majority of immune cells as well as on cells in the central nervous system (34).”
BackgroundCTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms
Parry, R. V., Chemnitz, J. M., Frauwirth, K. A., Lanfranco, A. R., Braunstein, I., Kobayashi, S. V., Linsley, P. S., Thompson, C. B., & Riley, J. L. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9543-9553.2005 · Cited by 1,931 · cited 4×
“ligation does not inhibit PI3K signaling (42) (Fig.”
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Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
Overview of the immune response
Chaplin, D. D. (2010) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2009.12.980 · Cited by 2,235
“In addition, a specific receptor-ligand pair, programmed death 1 and programmed death ligand 1, transduces signals to the activated lymphocyte to inhibit its proliferation and effector functions, thus extinguishing the Tcell response.(52) Mutations affecting the function of many of the molecules involved in intracellu…”
BackgroundThe PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300
“Engagement of PD1 by either of its ligands during TCR signaling can block T-cell proliferation, cytokine production and cytolytic function, and impair T-cell survival (19).”
BackgroundThe diverse functions of the PD1 inhibitory pathway
Sharpe, A. H., & Pauken, K. E. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.108 · Cited by 2,054
Metadata
- Authors
- Riley, J. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Riley, James L.
- ORCID
- Riley, James L.
- Venue
- Immunological Reviews
- Publisher
- Wiley
- Published
- 2009-04-21
- Volume
- 229
- Issue
- 1
- Pages
- 114-125
- ISSN
- 0105-2896 (ISSN-L)
- 1600-065X
- PMC
- PMC3424066
- OpenAlex
- W2017712207
- Cited by
- 778
- References
- 95
- Citations by year
- 2026: 21 · 2025: 39 · 2024: 37 · 2023: 66 · 2022: 73 · 2021: 84 · 2020: 64 · 2019: 61 · 2018: 60 · 2017: 49 · 2016: 33 · 2015: 41 · 2014: 34 · 2013: 37 · 2012: 30
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA113783, R01CA113783)
- National Institute of Allergy and Infectious Diseases (AI080192, P01AI080192, R01AI057838, AI057838, PD-1 PO1AI080192)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- PD-1 signaling, PDCD1, PD-L1, PD-L2, T cell exhaustion, T cell proliferation inhibition, cytotoxic T lymphocyte antigen 4, signal transduction, T cell differentiation, immune checkpoint, primary T cells
- MeSH terms
- Animals, Antigens, Surface, Humans, T-Lymphocytes, Signal Transduction, Antigens, CD, CD28 Antigens, Apoptosis Regulatory Proteins, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatase, Non-Receptor Type 11, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
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