The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
Chronic Virus Infection Enforces Demethylation of the Locus that Encodes PD-1 in Antigen-Specific CD8+ T Cells
Open accessAbstract
SUMMARY Functionally exhausted T cells express high levels of the PD-1 inhibitory receptor, and therapies that block PD-1 signaling show promise for resolving chronic viral infections and cancer. Using human and murine systems of acute and chronic viral infections we analyzed epigenetic regulation of PD-1 expression during CD8 T cell differentiation. During acute infection, naïve to effector CD8 T cell differentiation was accompanied by a transient loss of DNA methylation of the Pdcd1 locus that was directly coupled to the duration and strength of TCR signaling. Further differentiation into functional memory cells coincided with Pdcd1 remethylation providing an adapted program for regulation of PD-1 expression. In contrast, the Pdcd1 regulatory region was completely demethylated in exhausted CD8 T cells and remained unmethylated even when virus titers decreased. This lack of DNA remethylation leaves the Pdcd1 locus poised for rapid expression, potentially providing a signal for premature termination of antiviral functions.
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Citations
Cites
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BackgroundPD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
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Self-citationViral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
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Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity
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Self-citation
Cited by
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
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Self-citationEpigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
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De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
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Metadata
- Authors
- Youngblood, B., Oestreich, K. J., Ha, S.-J., Duraiswamy, J., Akondy, R. S., West, E. E., Wei, Z., Lu, P., Austin, J. W., Riley, J. L., Boss, J. M., & Ahmed, R.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 35
- Issue
- 3
- Pages
- 400-412
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1985182657
- Cited by
- 419
- References
- 13
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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