The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells
Open accessAbstract
Programmed Death-1 (PD-1) has received considerable attention as a key regulator of CD8+ T cell exhaustion during chronic infection and cancer because blockade of this pathway partially reverses T cell dysfunction. Although the PD-1 pathway is critical in regulating established “exhausted” CD8+ T cells (TEX cells), it is unclear whether PD-1 directly causes T cell exhaustion. We show that PD-1 is not required for the induction of exhaustion in mice with chronic lymphocytic choriomeningitis virus (LCMV) infection. In fact, some aspects of exhaustion are more severe with genetic deletion of PD-1 from the onset of infection. Increased proliferation between days 8 and 14 postinfection is associated with subsequent decreased CD8+ T cell survival and disruption of a critical proliferative hierarchy necessary to maintain exhausted populations long term. Ultimately, the absence of PD-1 leads to the accumulation of more cytotoxic, but terminally differentiated, CD8+ TEX cells. These results demonstrate that CD8+ T cell exhaustion can occur in the absence of PD-1. They also highlight a novel role for PD-1 in preserving TEX cell populations from overstimulation, excessive proliferation, and terminal differentiation.
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Citations
Cites
The blockade of immune checkpoints in cancer immunotherapy
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Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
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PD-1 and Its Ligands in Tolerance and Immunity
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“Furthermore, blockade of other inhibitory receptors alone and in combination with PD1– PDL1 blockade suggests that PD1 is the major inhibitory receptor controlling exhaustion (Blackburn et al., 2009; Kassu et al., 2010; Sakuishi et al., 2010; Wherry, 2011).”
BackgroundMethodInfluentialSelf-citationChimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
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Self-citationMolecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
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Self-citationTargeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
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Viral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
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Cited by
TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion
Khan, O., Giles, J. R., McDonald, S., Manne, S., Ngiow, S. F., Patel, K. P., Werner, M. T., Huang, A. C., Alexander, K. A., Wu, J. E., et al. (2019) · Nature · doi:10.1038/s41586-019-1325-x · Cited by 1,646
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Self-citationCRISPR-engineered T cells in patients with refractory cancer
Stadtmauer, E. A., Fraietta, J. A., Davis, M. M., Cohen, A. D., Weber, K. L., Lancaster, E., Mangan, P. A., Kulikovskaya, I., Gupta, M., Chen, F., et al. (2020) · Science · doi:10.1126/science.aba7365 · Cited by 1,478
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., et al. (2016) · Science · doi:10.1126/science.aaf2807 · Cited by 1,348
Self-citationThommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,299
Metadata
- Authors
- Odorizzi, P. M., Pauken, K. E., Paley, M. A., Sharpe, A., & Wherry, E. J.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-06-01
- Volume
- 212
- Issue
- 7
- Pages
- 1125-1137
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W1910384556
- Cited by
- 467
- References
- 18
- FWCI
- 15.39
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Odorizzi, P. M., Pauken, K. E., Paley, M. A., Sharpe, A., & Wherry, E. J. (2015). Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20142237
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
