The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Enhancing SIV-specific immunity in vivo by PD-1 blockade
Open accessAbstract
Chronic immunodeficiency virus infections are characterized by dysfunctional cellular and humoral antiviral immune responses. As such, immune modulatory therapies that enhance and/or restore the function of virus-specific immunity may protect from disease progression. Here we investigate the safety and immune restoration potential of blockade of the co-inhibitory receptor programmed death 1 (PD-1) during chronic simian immunodeficiency virus (SIV) infection in macaques. We demonstrate that PD-1 blockade using an antibody to PD-1 is well tolerated and results in rapid expansion of virus-specific CD8 T cells with improved functional quality. This enhanced T-cell immunity was seen in the blood and also in the gut, a major reservoir of SIV infection. PD-1 blockade also resulted in proliferation of memory B cells and increases in SIV envelope-specific antibody. These improved immune responses were associated with significant reductions in plasma viral load and also prolonged the survival of SIV-infected macaques. Blockade was effective during the early (week 10) as well as late (∼week 90) phases of chronic infection even under conditions of severe lymphopenia. These results demonstrate enhancement of both cellular and humoral immune responses during a pathogenic immunodeficiency virus infection by blocking a single inhibitory pathway and identify a novel therapeutic approach for control of human immunodeficiency virus infections.
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Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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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-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
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Cited by
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
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Redefining Chronic Viral Infection
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Self-citationWang, Z., Aguilar, E. G., Luna, J. I., Dunai, C., Khuat, L. T., Le, C. T., Mirsoian, A., Minnar, C. M., Stoffel, K. M., Sturgill, I. R., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0221-5 · Cited by 865
Metadata
- Authors
- Velu, V., Titanji, K., Zhu, B., Husain, S., Pladevega, A., Lai, L., Vanderford, T. H., Chennareddi, L., Silvestri, G., Freeman, G. J., Ahmed, R., & Amara, R. R.
- Venue
- Nature
- Published
- 2008-12-10
- Volume
- 458
- Issue
- 7235
- Pages
- 206-210
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2058798829
- Cited by
- 771
- References
- 7
- FWCI
- 13.55
- Type
- journal article
- Language
- en
- Open access
- green
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- Velu, V., Titanji, K., Zhu, B., Husain, S., Pladevega, A., Lai, L., Vanderford, T. H., Chennareddi, L., Silvestri, G., Freeman, G. J., Ahmed, R., & Amara, R. R. (2009). Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature. https://doi.org/10.1038/nature07662
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