The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Strength of PD-1 signaling differentially affects T-cell effector functions
Open accessAbstract
High surface expression of programmed death 1 (PD-1) is associated with T-cell exhaustion; however, the relationship between PD-1 expression and T-cell dysfunction has not been delineated. We developed a model to study PD-1 signaling in primary human T cells to study how PD-1 expression affected T-cell function. By determining the number of T-cell receptor/peptide-MHC complexes needed to initiate a Ca 2+ flux, we found that PD-1 ligation dramatically shifts the dose–response curve, making T cells much less sensitive to T-cell receptor–generated signals. Importantly, other T-cell functions were differentially sensitive to PD-1 expression. We observed that high levels of PD-1 expression were required to inhibit macrophage inflammatory protein 1 beta production, lower levels were required to block cytotoxicity and IFN-γ production, and very low levels of PD-1 expression could inhibit TNF-α and IL-2 production as well as T-cell expansion. These findings provide insight into the role of PD-1 expression in enforcing T-cell exhaustion and the therapeutic potential of PD-1 blockade.
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Citations
Cites
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
PD-1 and Its Ligands in Tolerance and Immunity
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“This continued presence of antigen subverts normal memory T-cell generation and leads effector T cells down a path of exhaustion in which they sequentially lose effector function (2).”
BackgroundInfluentialPD-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
Self-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
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PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection
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PD-1 signaling in primary T cells
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“Proc Natl Acad Sci USA 108(22):9196–9201.”
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Self-citation
Cited by
Identification of CMTM6 and CMTM4 as PD-L1 protein regulators
Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., Logtenberg, M. E. W., Slagter, M., Rozeman, E. A., Hofland, I., et al. (2017) · Nature · doi:10.1038/nature23669 · Cited by 697
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Resistance to PD1/PDL1 checkpoint inhibition
O'Donnell, J. S., Long, G. V., Scolyer, R. A., Teng, M. W. L., & Smyth, M. J. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.11.007 · Cited by 572
Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond
Ai, L., Xu, A., & Xu, J. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-15-3266-5_3 · Cited by 526
PD‐1/PD‐L1 pathway: Basic biology and role in cancer immunotherapy
Salmaninejad, A., Valilou, S. F., Shabgah, A. G., Aslani, S., Alimardani, M., Pasdar, A., & Sahebkar, A. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28358 · Cited by 445
Metadata
- Authors
- Wei, F., Zhong, S., Ma, Z., Kong, H., Medvec, A., Ahmed, R., Freeman, G. J., Krogsgaard, M., & Riley, J. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-04-22
- Volume
- 110
- Issue
- 27
- Pages
- E2480-9
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2093463728
- Cited by
- 304
- References
- 10
- FWCI
- 10.38
- Type
- journal article
- Language
- en
- Open access
- green
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- Wei, F., Zhong, S., Ma, Z., Kong, H., Medvec, A., Ahmed, R., Freeman, G. J., Krogsgaard, M., & Riley, J. L. (2013). Strength of PD-1 signaling differentially affects T-cell effector functions. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1305394110
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