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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Cites
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Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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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-citationGenomic DNA methylation: the mark and its mediators.
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Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
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Self-citationViral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
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“…profile in memory CD8+ T cells is due to remethylation rather than selective death of terminal effector cells, we measured the methylation status in day 8 terminal effector (Klrg1hiIL7Ralo) and memory precursor (Klrg1loIL7Rahi) subsets (Figure 2D; Kaech et al., 2003; Sarkar et al., 2008).”
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BackgroundSelf-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
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PD-1 and PD-1 ligands: from discovery to clinical application
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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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- The paper
- 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. (2011). Chronic Virus Infection Enforces Demethylation of the Locus that Encodes PD-1 in Antigen-Specific CD8+ T Cells. Immunity. https://doi.org/10.1016/j.immuni.2011.06.015
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