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Chronic Virus Infection Enforces Demethylation of the Locus that Encodes PD-1 in Antigen-Specific CD8+ T Cells
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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
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
Sallusto, F., Lenig, D., Förster, R., Lipp, M., & Lanzavecchia, A. (1999) · Nature · doi:10.1038/44385 · Cited by 5,846 · cited 1×
“Human CD8+ T cells were obtained from PBMCs of healthy human donors and sorted to a purity of ptember 23, 2011 ª2011 Elsevier Inc. 407 >94% (Figure S5; Day et al., 2006; Sallusto et al., 1999; J.D. and R.A., unpublished results).”
BackgroundPD-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-citationGenomic DNA methylation: the mark and its mediators.
Klose, R. J., & Bird, A. P. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.008 · Cited by 2,501
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103
Self-citationViral Immune Evasion Due to Persistence of Activated T Cells Without Effector Function
Zajac, A. J., Blattman, J. N., Murali-Krishna, K., Sourdive, D. J. D., Suresh, M., Altman, J. D., & Ahmed, R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2205 · Cited by 1,978
Self-citationKaech, S. M., Tan, J. T., Wherry, E. J., Konieczny, B. T., Surh, C. D., & Ahmed, R. (2003) · Nature Immunology · doi:10.1038/ni1009 · Cited by 1,830 · cited 4×
“…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).”
BackgroundResultInfluentialSelf-citationImmunological memory and protective immunity: understanding their relation
Ahmed, R., & Gray, D. (1996) · Science · doi:10.1126/science.272.5258.54 · Cited by 1,775 · cited 1×
“After clearance of the pathogen, the antigen-specific cell population shifts to a state of prepared- ness with the emergence of highly functional memory cells (Ahmed and Gray, 1996; Bevan and Goldrath, 2000; Lefrancois and Masopust, 2002).”
BackgroundSelf-citationUpregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction
Trautmann, L., Janbazian, L., Chomont, N., Said, E. A., Gimmig, S., Bessette, B., Boulassel, M.-R., Delwart, E., Sepulveda, H., Balderas, R. S., et al. (2006) · Nature Medicine · doi:10.1038/nm1482 · Cited by 1,565
PD-1 and PD-1 ligands: from discovery to clinical application
Okazaki, T., & Honjo, T. (2007) · International Immunology · doi:10.1093/intimm/dxm057 · Cited by 1,310
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
Blank, C. U., Haining, W. N., Held, W., Hogan, P. G., Kallies, A., Lugli, E., Lynn, R. C., Philip, M., Rao, A., Restifo, N. P., et al. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0221-9 · Cited by 1,603
Self-citationEpigenetic 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
De Novo Epigenetic Programs Inhibit PD-1 Blockade-Mediated T Cell Rejuvenation
Ghoneim, H. E., Fan, Y., Moustaki, A., Abdelsamed, H. A., Dash, P., Dogra, P., Carter, R., Awad, W., Neale, G., Thomas, P. G., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.007 · Cited by 781
Self-citationSchietinger, A., Philip, M., Krisnawan, V. E., Chiu, E. Y., Delrow, J. J., Basom, R. S., Lauer, P., Brockstedt, D. G., Knoblaugh, S. E., Hämmerling, G. J., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.011 · Cited by 720
Yang, H., Bueso-Ramos, C., DiNardo, C., Estecio, M. R., Davanlou, M., Geng, Q.-R., Fang, Z., Nguyen, M., Pierce, S., Wei, Y., et al. (2014) · Leukemia · doi:10.1038/leu.2013.355 · Cited by 688
Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends
Sun, Q., Hong, Z., Zhang, C., Wang, L., Han, Z., & Ma, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01522-4 · Cited by 598
Effector CD8 T cells dedifferentiate into long-lived memory cells
Youngblood, B., Hale, J. S., Kissick, H. T., Ahn, E., Xu, X., Wieland, A., Araki, K., West, E. E., Ghoneim, H. E., Fan, Y., et al. (2017) · Nature · doi:10.1038/nature25144 · Cited by 471
Self-citationPD‐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
The emerging role of epigenetic therapeutics in immuno-oncology
Topper, M. J., Vaz, M., Marrone, K. A., Brahmer, J. R., & Baylin, S. B. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0266-5 · Cited by 433
Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
Prinzing, B., Zebley, C. C., Petersen, C. T., Fan, Y., Anido, A. A., Yi, Z., Nguyen, P., Houke, H., Bell, M., Haydar, D., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abh0272 · Cited by 349
Self-citationFBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells
Meng, X., Liu, X., Guo, X., Jiang, S., Chen, T., Hu, Z., Liu, H., Bai, Y., Xue, M., Hu, R., et al. (2018) · Nature · doi:10.1038/s41586-018-0756-0 · Cited by 303
Weng, N.-P., Araki, Y., & Subedi, K. (2012) · Nature Reviews Immunology · doi:10.1038/nri3173 · Cited by 290
Pascual-García, M., Bonfill-Teixidor, E., Planas-Rigol, E., Rubio-Perez, C., Iurlaro, R., Arias, A., Cuartas, I., Sala-Hojman, A., Escudero, L., Martínez-Ricarte, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10369-9 · Cited by 262
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237
Viral acute lower respiratory infections impair CD8+ T cells through PD-1
Erickson, J. J., Gilchuk, P., Hastings, A. K., Tollefson, S. J., Johnson, M., Downing, M. B., Boyd, K. L., Johnson, J. E., Kim, A. S., Joyce, S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci62860 · Cited by 203
Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1
Chamoto, K., Yaguchi, T., Tajima, M., & Honjo, T. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00867-9 · Cited by 185
CXCR3 enables recruitment and site-specific bystander activation of memory CD8(+) T cells
Maurice, N. J., McElrath, M. J., Andersen-Nissen, E., Frahm, N., & Prlic, M. (2019) · Nature Communications · doi:10.1038/s41467-019-12980-2 · Cited by 117
Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells.
Youngblood, B., Wherry, E. J., & Ahmed, R. (2012) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0b013e32834ddcf2 · Cited by 68
Self-citationZeidan, A. M., Boss, I., Beach, C. L., Copeland, W. B., Thompson, E., Fox, B. A., Hasle, V. E., Ogasawara, K., Cavenagh, J., Silverman, L. R., et al. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021005487 · Cited by 61
Epigenetic mechanisms of tumor resistance to immunotherapy
Arenas-Ramirez, N., Sahin, D., & Boyman, O. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2908-7 · Cited by 36
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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