PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

Petrovas, Constantinos; Casazza, Joseph P.; Brenchley, Jason M.; Price, David A.; Gostick, Emma; Adams, William C.; Precopio, Melissa L.; Schacker, Timothy; Roederer, Mario; Douek, Daniel C.; Koup, Richard A.

doi:10.1084/jem.20061496

Cited by 889T-cell and B-cell ImmunologyHIV Research and TreatmentCancer Immunotherapy and Biomarkers

PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

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Petrovas, Constantinos, Casazza, Joseph P., Brenchley, Jason M., Price, David A., Gostick, Emma, Adams, William C., Precopio, Melissa L., Schacker, Timothy +3 more·2006·The Journal of Experimental Medicine

DOI 10.1084/jem.20061496PMC PMC2118095

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Abstract

Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8+ T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8+ T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8+ T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8+ T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8+ T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8+ T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8+ T cell numbers, but possibly not all functions in vivo.

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The view that many late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels.
“The view that many of these late-stage differentiated cells are not dysfunctional or senescent is supported by studies showing that the inhibitory molecule programmed death-1 (PD-1) is expressed on very few CMV-specific cells and at low levels (Petrovas et al. 2006; Trautmann et al. 2006).”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Petrovas et al. 2006

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Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 3,960 · see citing works
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Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259 · see citing works
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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 · see citing works
Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome
Koup, R. A., Safrit, J. T., Cao, Y., Andrews, C. A., McLeod, G. X., Borkowsky, W., Farthing, C., & Ho, D. D. (1994) · Journal of Virology · doi:10.1128/jvi.68.7.4650-4655.1994 · Cited by 2,494 · see citing works
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Tseng, S.-Y., Otsuji, M., Gorski, K. S., Huang, X., Slansky, J. E., Pai, S. I., Shalabi, A., Shin, T., Pardoll, D. M., & Tsuchiya, H. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.7.839 · Cited by 867 · see citing works
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Kadowaki, N., Antonenko, S. V., Lau, J. Y., & Liu, Y.-J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.219 · Cited by 847 · see citing works
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Fonteneau, J., Larsson, M., Beignon, A., McKenna, K., DaSilva, I., Amara, A., Liu, Y.-J., Lifson, J. D., Littman, D. R., & Bhardwaj, N. (2004) · Journal of Virology · doi:10.1128/jvi.78.10.5223-5232.2004 · Cited by 351 · see citing works
Loss of HIV-1–specific CD8+ T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-induced HIV-1–specific CD4+ T Cells
Lichterfeld, M. D., Kaufmann, D., Yu, X. G., Mui, S. K., Addo, M. M., Johnston, M. N., Cohen, D., Robbins, G. K., Pae, E., Alter, G., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041270 · Cited by 338 · see citing works
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Zimmerli, S. C., Harari, A., Cellerai, C., Vallelian, F., Bart, P., & Pantaleo, G. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502393102 · Cited by 307 · see citing works
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Rothstein, D. M., & Sayegh, M. H. (2003) · Immunological Reviews · doi:10.1046/j.1600-065x.2003.00088.x · Cited by 220 · see citing works
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Loré, K., Smed‐Sörensen, A., Vasudevan, J., Mascola, J. R., & Koup, R. A. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042413 · Cited by 209 · see citing works
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Johnson, W. E., & Desrosiers, R. C. (2002) · Annual Review of Medicine · doi:10.1146/annurev.med.53.082901.104053 · Cited by 183 · see citing works
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Serghides, L., Bukczynski, J., Wen, T., Wang, C., Routy, J., Boulassel, M., Sékaly, R., Ostrowski, M., Bernard, N. F., & Watts, T. H. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6368 · Cited by 72 · see citing works
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Petrovas, C., Mueller, Y. M., Dimitriou, I. D., Bojczuk, P. M., Mounzer, K., Witek, J., Altman, J. D., & Katsikis, P. D. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.7.4444 · Cited by 58 · see citing works
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OX40 Ligation of CD4+ T Cells Enhances Virus-Specific CD8+ T Cell Memory Responses Independently of IL-2 and CD4+ T Regulatory Cell Inhibition
Yu, Q., Yue, F. Y., Gu, X. X. J., Schwartz, H., Kovacs, C. M., & Ostrowski, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2486 · Cited by 45 · see citing works
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Keir, M. E., Butte, M. J., Freeman, G. J., & Sharpe, A. H. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090331 · Cited by 5,378 · see citing works
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Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection
Blackburn, S. D., Shin, H., Haining, W. N., Zou, T., Workman, C. J., Polley, A., Betts, M. R., Freeman, G. J., Vignali, D. A. A., & Wherry, E. J. (2009) · Nature Immunology · doi:10.1038/ni.1679 · Cited by 2,062 · see citing works
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Douek, D. C., Roederer, M., & Koup, R. A. (2008) · Annual Review of Medicine · doi:10.1146/annurev.med.60.041807.123549 · Cited by 612 · see citing works
Self-citation
The PD1:PD-L1/2 Pathway from Discovery to Clinical Implementation
Bardhan, K., Anagnostou, T., & Boussiotis, V. A. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00550 · Cited by 606 · see citing works
Lytic Granule Loading of CD8+ T Cells Is Required for HIV-Infected Cell Elimination Associated with Immune Control
Migueles, S. A., Osborne, C. M., Royce, C., Compton, A. A., Joshi, R. P., Weeks, K. A., Rood, J. E., Berkley, A. M., Sacha, J. B., Cogliano-Shutta, N. A., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.10.010 · Cited by 586 · see citing works
Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway
Liu, J., Hamrouni, A., Wołowiec, D., Coiteux, V., Kuliczkowski, K., Hétuin, D., Saudemont, A., & Quesnel, B. (2007) · Blood · doi:10.1182/blood-2006-10-051482 · Cited by 580 · see citing works
Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade
Blackburn, S. D., Shin, H., Freeman, G. J., & Wherry, E. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801497105 · Cited by 575 · see citing works
PD-1 Is Expressed by Tumor-Infiltrating Immune Cells and Is Associated with Poor Outcome for Patients with Renal Cell Carcinoma
Thompson, R. H., Dong, H., Lohse, C. M., Leibovich, B. C., Blute, M. L., Cheville, J. C., & Kwon, E. D. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2599 · Cited by 569 · see citing works
Immune checkpoint blockade in infectious diseases
Wykes, M., & Lewin, S. R. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.112 · Cited by 569 · see citing works
Second messenger role for Mg2+ revealed by human T-cell immunodeficiency
Li, F.-Y., Chaigne-Delalande, B., Kanellopoulou, C., Davis, J. C., Matthews, H. F., Douek, D. C., Cohen, J. I., Uzel, G., Su, H. C., & Lenardo, M. J. (2011) · Nature · doi:10.1038/nature10246 · Cited by 564 · see citing works
Self-citation
Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family
Schildberg, F. A., Klein, S. R., Freeman, G. J., & Sharpe, A. H. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.002 · Cited by 537 · see citing works
Immune checkpoints and their inhibition in cancer and infectious diseases
Dyck, L., & Mills, K. H. G. (2017) · European Journal of Immunology · doi:10.1002/eji.201646875 · Cited by 541 · see citing works
Selective effects of PD-1 on Akt and Ras pathways regulate molecular components of the cell cycle and inhibit T cell proliferation
Patsoukis, N., Brown, J., Petkova, V., Liu, F., Li, L., & Boussiotis, V. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002796 · Cited by 529 · see citing works
Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction
Kaufmann, D., Kavanagh, D. G., Pereyra, F., Zaunders, J. J., Mackey, E. W., Miura, T., Palmer, S., Brockman, M. A., Rathod, A., Trocha, A. K., et al. (2007) · Nature Immunology · doi:10.1038/ni1515 · Cited by 522 · see citing works
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF
Quigley, M. M., Pereyra, F., Nilsson, B., Porichis, F., Fonseca, C., Eichbaum, Q. G., Jülg, B. D., Jesneck, J. L., Brosnahan, K., Imam, S., et al. (2010) · Nature Medicine · doi:10.1038/nm.2232 · Cited by 505 · see citing works
The Common γ-Chain Cytokines IL-2, IL-7, IL-15, and IL-21 Induce the Expression of Programmed Death-1 and Its Ligands
Kinter, A. L., Godbout, E. J., McNally, J. P., Sereti, I., Roby, G. A., O’Shea, M. A., & Fauci, A. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.6738 · Cited by 513 · see citing works
Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion
Blank, C. U., & Mackensen, A. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0272-1 · Cited by 502 · see citing works
Antiviral Intrahepatic T-Cell Responses Can Be Restored by Blocking Programmed Death-1 Pathway in Chronic Hepatitis B
Fisicaro, P., Valdatta, C., Massari, M., Loggi, E., Biasini, E., Sacchelli, L., Cavallo, M. C., Silini, E. M., Andreoné, P., Missale, G., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.09.052 · Cited by 490 · see citing works
Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?
Akbar, A. N., & Henson, S. M. (2011) · Nature Reviews Immunology · doi:10.1038/nri2959 · Cited by 474 · see citing works
Liver-Infiltrating Lymphocytes in Chronic Human Hepatitis C Virus Infection Display an Exhausted Phenotype with High Levels of PD-1 and Low Levels of CD127 Expression
Radziewicz, H., Ibegbu, C., Fernandez, M. L., Workowski, K., Obideen, K. M., Wehbi, M. A., Hanson, H. L., Steinberg, J. P., Masopust, D., Wherry, E. J., et al. (2006) · Journal of Virology · doi:10.1128/jvi.02021-06 · Cited by 482 · see citing works
Programmed death-1–induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection
Said, E. A., Dupuy, F. P., Trautmann, L., Zhang, Y., Shi, Y., Far, M. E., Hill, B. J., Noto, A., Ancuța, P., Peretz, Y., et al. (2010) · Nature Medicine · doi:10.1038/nm.2106 · Cited by 474 · see citing works
Self-citation
Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells
Odorizzi, P. M., Pauken, K. E., Paley, M., Sharpe, A. H., & Wherry, E. J. (2015) · The Journal of Experimental Medicine · doi:10.1084/jem.20142237 · Cited by 464 · see citing works
Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
Nikolich-Žugich, J. (2008) · Nature reviews. Immunology · doi:10.1038/nri2318 · Cited by 463 · see citing works
Pathogenic Mechanisms of HIV Disease
Moir, S. L., Chun, T., & Fauci, A. S. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130254 · Cited by 468 · see citing works
Impact of MHC class I diversity on immune control of immunodeficiency virus replication
Goulder, P., & Watkins, D. I. (2008) · Nature reviews. Immunology · doi:10.1038/nri2357 · Cited by 453 · see citing works
Immune activation and HIV persistence: implications for curative approaches to HIV infection
Klatt, N. R., Chomont, N., Douek, D. C., & Deeks, S. G. (2013) · Immunological Reviews · doi:10.1111/imr.12065 · Cited by 439 · see citing works
Self-citation
PD-1 and its ligands in T-cell immunity
Keir, M. E., Francisco, L. M., & Sharpe, A. H. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.04.012 · Cited by 432 · see citing works
T‐cell exhaustion in HIV infection
Fenwick, C. W., Joo, V., Jacquier, P., Noto, A., Banga, R., Perreau, M., & Pantaleo, G. (2019) · Immunological Reviews · doi:10.1111/imr.12823 · Cited by 412 · see citing works
CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART
Fromentin, R., Bakeman, W., Lawani, M. B., Khoury, G., Hartogensis, W., DaFonseca, S., Killian, M. L., Epling, L., Hoh, R., Sinclair, E., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005761 · Cited by 418 · see citing works
IFN-γ and TNF-α differentially regulate immunomodulation by murine mesenchymal stem cells
English, K., Barry, F., Field-Corbett, C., & Mahon, B. P. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.04.001 · Cited by 417 · see citing works
NFATc1 Regulates PD-1 Expression upon T Cell Activation
Oestreich, K. J., Yoon, H., Ahmed, R., & Boss, J. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.7.4832 · Cited by 416 · see citing works
Host-directed therapies for infectious diseases: current status, recent progress, and future prospects
Zumla, A. I., Rao, M., Wallis, R. S., Kaufmann, S. H. E., Rustomjee, R., Mwaba, P., Vilaplana, C., Yeboah‐Manu, D., Chakaya, J. M., Ippolito, G., et al. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)00078-5 · Cited by 408 · see citing works
PD-1–PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma
Yamamoto, R., Nishikori, M., Kitawaki, T., Sakai, T., Hishizawa, M., Tashima, M., Kondo, T., Ohmori, K., Kurata, M., Hayashi, T., et al. (2008) · Blood · doi:10.1182/blood-2007-05-085159 · Cited by 398 · see citing works
Reinvigorating exhausted HIV-specific T cells via PD-1–PD-1 ligand blockade
Freeman, G. J., Wherry, E. J., Ahmed, R., & Sharpe, A. H. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061800 · Cited by 400 · see citing works
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells
Gupta, P., Godec, J., Wolski, D., Adland, E., Yates, K. B., Pauken, K. E., Cosgrove, C., Ledderose, C., JUNGER, W. G., Robson, S. C., et al. (2015) · PLoS Pathogens · doi:10.1371/journal.ppat.1005177 · Cited by 384 · see citing works
PD-1 expression on tumor-specific T cells: Friend or foe for immunotherapy?
Simon, S., & Labarrière, N. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1364828 · Cited by 399 · see citing works
T Cell Exhaustion
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
CD8+ T cell efficacy in vaccination and disease
Appay, V., Douek, D. C., & Price, D. A. (2008) · Nature Medicine · doi:10.1038/nm.f.1774 · Cited by 393 · see citing works
Self-citation
Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade
Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M. E., Kaminski, M., Gostick, E., Price, D. A., Freeman, G. J., Wherry, E. J., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000313 · Cited by 380 · see citing works
Self-citation
CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1
Fourcade, J., Sun, Z., Pagliano, O., Guillaume, P., Luescher, I. F., Sander, C., Kirkwood, J. M., Olive, D., Kuchroo, V., & Zarour, H. M. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2637 · Cited by 372 · see citing works
Upregulation of PD-1 Expression on Circulating and Intrahepatic Hepatitis C Virus-Specific CD8+T Cells Associated with Reversible Immune Dysfunction
Golden‐Mason, L., Palmer, B. E., Klarquist, J. S., Mengshol, J. A., Castelblanco, N., & Rosen, H. R. (2007) · Journal of Virology · doi:10.1128/jvi.00409-07 · Cited by 371 · see citing works
Defective HIV-1 proviruses are expressed and can Be recognized by cytotoxic T lymphocytes, which shape the proviral landscape
Pollack, R. A., Jones, R. B., Pertea, M., Bruner, K. M., Martin, A. R., Thomas, A. S., Capoferri, A. A., Beg, S. A., Huang, S.-H., Karandish, S., et al. (2017) · Cell Host & Microbe · doi:10.1016/j.chom.2017.03.008 · Cited by 370 · see citing works
Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers
Liu, Y., Cheng, Y., Xu, Y., Wang, Z., Du, X., Li, C., Peng, J., Gao, L., Liang, X., & Ma, C. (2017) · Oncogene · doi:10.1038/onc.2017.209 · Cited by 367 · see citing works
T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses
Saeidi, A., Zandi, K., Cheok, Y. Y., Saeidi, H., Wong, W. F., Lee, C. Y. Q., Cheong, H. C., Yong, Y. K., Larsson, M., & Shankar, E. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02569 · Cited by 346 · see citing works
CD8 T cell dysfunction during chronic viral infection
Shin, H., & Wherry, E. J. (2007) · Current Opinion in Immunology · doi:10.1016/j.coi.2007.06.004 · Cited by 346 · see citing works
Targeting the Latent Reservoir for HIV-1
Sengupta, S., & Siliciano, R. F. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.030 · Cited by 333 · see citing works
The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer
Muenst, S. E., Soysal, S. D., Gao, F., Obermann, E. C., Oertli, D., & Gillanders, W. E. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2581-3 · Cited by 332 · see citing works
CD4 T Cells Promote Rather than Control Tuberculosis in the Absence of PD-1–Mediated Inhibition
Barber, D. L., Mayer-Barber, K. D., Feng, C. G., Sharpe, A. H., & Sher, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1003304 · Cited by 329 · see citing works
Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients
Guignant, C., Lepape, A., Huang, X., Kherouf, H., Denis, L., Poitevin, F., Malcus, C., Gouél‐Cheron, A., Allaouchiche, B., Gueyffier, F., et al. (2011) · Critical Care · doi:10.1186/cc10112 · Cited by 323 · see citing works
T cell exhaustion during persistent viral infections
Kahan, S. M., Wherry, E. J., & Zajac, A. J. (2015) · Virology · doi:10.1016/j.virol.2014.12.033 · Cited by 321 · see citing works
Role of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection
González, S. M., Taborda, N. A., & Rugeles, M. T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00936 · Cited by 323 · see citing works
Early Events in Sexual Transmission of HIV and SIV and Opportunities for Interventions
Haase, A. T. (2010) · Annual Review of Medicine · doi:10.1146/annurev-med-080709-124959 · Cited by 322 · see citing works
CD8+ T cell exhaustion
Kurachi, M. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-019-00744-5 · Cited by 317 · see citing works
Role of PD-1 in Regulating T-Cell Immunity
Jin, H., Ahmed, R., & Okazaki, T. (2010) · Current topics in microbiology and immunology · doi:10.1007/82_2010_116 · Cited by 303 · see citing works
Strength of PD-1 signaling differentially affects T-cell effector functions
Wei, F., Zhong, S., Ma, Z., Kong, H., Medvec, A. R., Ahmed, R., Freeman, G. J., Krogsgaard, M., & Riley, J. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305394110 · Cited by 306 · see citing works
Immune Checkpoint Proteins: A New Therapeutic Paradigm for Cancer—Preclinical Background: CTLA-4 and PD-1 Blockade
Weber, J. S. (2010) · Seminars in Oncology · doi:10.1053/j.seminoncol.2010.09.005 · Cited by 303 · see citing works
Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis
Brahmamdam, P., Inoue, S., Unsinger, J., Chang, K. C., McDunn, J. E., & Hotchkiss, R. S. (2010) · Journal of Leukocyte Biology · doi:10.1189/jlb.0110037 · Cited by 303 · see citing works
CD8+ T cells in HIV control, cure and prevention
Collins, D. R., Gaiha, G. D., & Walker, B. D. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0274-9 · Cited by 305 · see citing works
PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors
Zhang, J., Zhang, Z., Wang, X., Fu, J., Yao, J., Jiao, Y., Chen, L., Zhang, H., Wei, J., Jin, L., et al. (2007) · Blood · doi:10.1182/blood-2006-09-044826 · Cited by 298 · see citing works
PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells
West, E. E., Jin, H., Rasheed, A. U., Penaloza‐MacMaster, P., Ha, S., Tan, W. G., Youngblood, B., Freeman, G. J., Smith, K. A., & Ahmed, R. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67008 · Cited by 293 · see citing works
T-bet and Eomes Are Differentially Linked to the Exhausted Phenotype of CD8+ T Cells in HIV Infection
Buggert, M., Tauriainen, J., Yamamoto, T., Frederiksen, J., Ivarsson, M. A., Michaëlsson, J., Lund, O., Hejdeman, B., Jansson, M., Sönnerborg, A. B., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004251 · Cited by 293 · see citing works
Self-citation
Features of responding T cells in cancer and chronic infection
Kim, P. S., & Ahmed, R. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.02.005 · Cited by 296 · see citing works
Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice
Brainard, D. M., Seung, E., Frahm, N., Cariappa, A., Bailey, C. C., Hart, W. K., Shin, H., Brooks, S. F., Knight, H., Eichbaum, Q. G., et al. (2009) · Journal of Virology · doi:10.1128/jvi.02207-08 · Cited by 285 · see citing works
HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
Boasso, A., Herbeuval, J., Hardy, A. W., Anderson, S. A., Dolan, M. J., Fuchs, D., & Shearer, G. M. (2006) · Blood · doi:10.1182/blood-2006-07-034785 · Cited by 286 · see citing works
IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells
Brockman, M. A., Kwon, D. S., Tighe, D. P., Pavlik, D. F., Rosato, P. C., Sela, J., Porichis, F., Gall, S. L., Waring, M. T., Moss, K., et al. (2009) · Blood · doi:10.1182/blood-2008-12-191296 · Cited by 285 · see citing works
Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection
Penna, A., Pilli, M., Zerbini, A., Orlandini, A., Mezzadri, S., Sacchelli, L., Missale, G., & Ferrari, C. I. (2007) · Hepatology · doi:10.1002/hep.21541 · Cited by 287 · see citing works
The growth and potential of human antiviral monoclonal antibody therapeutics
Marasco, W. A., & Sui, J. (2007) · Nature Biotechnology · doi:10.1038/nbt1363 · Cited by 284 · see citing works
The PD-1/PD-L1 Axis and Virus Infections: A Delicate Balance
Schönrich, G., & Raftery, M. J. (2019) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2019.00207 · Cited by 272 · see citing works
Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo
Tinoco, R., Alcalde, V., Yang, Y., Sauer, K., & Zúñiga, E. I. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.015 · Cited by 260 · see citing works
Programmed Death 1 Expression on HIV-Specific CD4+ T Cells Is Driven by Viral Replication and Associated with T Cell Dysfunction
D’Souza, M., Fontenot, A. P., Mack, D. G., Lozupone, C., Dillon, S. M., Meditz, A. L., Wilson, C. C., Connick, E., & Palmer, B. E. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.3.1979 · Cited by 260 · see citing works
Emerging Tim-3 functions in antimicrobial and tumor immunity
Sakuishi, K., Jayaraman, P., Behar, S. M., Anderson, A. C., & Kuchroo, V. K. (2011) · Trends in Immunology · doi:10.1016/j.it.2011.05.003 · Cited by 258 · see citing works
Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients
Zhang, Y., Li, J., Lou, J., Zhou, Y., Bo, L., Zhu, J., Zhu, K., Wan, X., Cai, Z., & Deng, X. (2011) · Critical Care · doi:10.1186/cc10059 · Cited by 258 · see citing works
Programmed Death (PD)-1:PD-Ligand 1/PD-Ligand 2 Pathway Inhibits T Cell Effector Functions during Human Tuberculosis
Jurado, J. O., Alvarez, I. B., Pasquinelli, V., Martínez, G., Quiroga, M. F., Abbate, E. H., Musella, R. M., Chuluyán, E., & García, V. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.116 · Cited by 257 · see citing works
Costimulatory and Coinhibitory Receptor Pathways in Infectious Disease
Attanasio, J., & Wherry, E. J. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.022 · Cited by 256 · see citing works
Enhancing Virus-Specific Immunity In Vivo by Combining Therapeutic Vaccination and PD-L1 Blockade in Chronic Hepadnaviral Infection
Liu, J., Zhang, E., Ma, Z., Wu, W., Kosinska, A. D., Zhang, X., Möller, I., Seiz, P. L., Glebe, D., Wang, B., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1003856 · Cited by 252 · see citing works
Phenotype, Function, and Gene Expression Profiles of Programmed Death-1hi CD8 T Cells in Healthy Human Adults
Duraiswamy, J., Ibegbu, C., Masopust, D., Miller, J. D., Araki, K., Doho, G., Tata, P., Sk, G., Zilliox, M. J., Nakaya, H. I., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1001783 · Cited by 246 · see citing works
PD-1 Regulates Self-Reactive CD8+ T Cell Responses to Antigen in Lymph Nodes and Tissues
Keir, M. E., Freeman, G. J., & Sharpe, A. H. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5064 · Cited by 243 · see citing works
Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8+ T Cells
Streeck, H., Brumme, Z. L., Anastario, M. P., Cohen, K. W., Jolin, J. S., Meier, A., Brumme, C. J., Rosenberg, E. S., Alter, G., Allen, T. M., et al. (2008) · PLoS Medicine · doi:10.1371/journal.pmed.0050100 · Cited by 241 · see citing works

ARTICLE PD-1 is a regulator of virus-specific CD8 + T cell survival in HIV infection
Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Emma Gostick, D., Adams, W. C., Precopio, M. L., Schacker, T. W., Roederer, M., Douek, D. C., et al. (2013)
Self-citation
Human immunodeficiency virus (HIV-1) infection selectively downregulates PD-1 expression in infected cells and protects the cells from early apoptosis in vitro and in vivo
Venkatachari, N. J., Buchanan, W. G., & Ayyavoo, V. (2008) · Virology · doi:10.1016/j.virol.2008.03.015 · Cited by 24 · see citing works
PD-1 expression on memory CD8 and CD4 T-cell subsets in healthy humans (43.43)
Duraiswamy, J., Miller, J. D., Masopust, D., Ibegbu, C., Wu, H., Freeman, G. J., & Ahmed, R. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.supp.43.43 · Cited by 3 · see citing works
Differential Association of Programmed Death-1 and CD57 with Ex Vivo Survival of CD8+ T Cells in HIV Infection
Petrovas, C., Chaon, B., Ambrozak, D. R., Price, D. A., Melenhorst, J. J., Hill, B. J., Geldmacher, C., Casazza, J. P., Chattopadhyay, P. K., Roederer, M., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900182 · Cited by 114 · see citing works
Self-citation
Upregulation 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 · see citing works

Authors: Petrovas, C., Casazza, J. P., Brenchley, J. M., Price, D. A., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., & Koup, R. A.
Affiliations: 1Immunology Laboratory
2Human Immunology Section,
John Radcliffe Hospital (GB)
3Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK
University of Minnesota (US)
National Institutes of Health (US)
ORCID: Petrovas, Constantinos
Casazza, Joseph P.
Brenchley, Jason M.
Price, David A.
Schacker, Timothy
Roederer, Mario
Douek, Daniel C.
Koup, Richard A.
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2006-09-05
Volume: 203
Issue: 10
Pages: 2281-2292
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.20061496
PMC: PMC2118095
OpenAlex: W2119146367
Cited by: 889
References: 48
Citations by year: 2026: 13 · 2025: 16 · 2024: 19 · 2023: 18 · 2022: 29 · 2021: 35 · 2020: 45 · 2019: 39 · 2018: 36 · 2017: 33 · 2016: 35 · 2015: 33 · 2014: 44 · 2013: 48 · 2012: 48
FWCI: 30.78
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: The Journal of Experimental Medicine (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
Funders: National Institute of Allergy and Infectious Diseases (P01AI074340)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: PD-1, HIV infection, CD8+ T cells, virus-specific T cells, T cell survival, apoptosis, memory T cells, cytomegalovirus, vaccinia virus, T cell proliferation, cytokine production, chronic viral infection, antiviral immunity
MeSH terms: Cell Survival, Flow Cytometry, Humans, HIV Infections, Antigens, CD, Apoptosis, CD8-Positive T-Lymphocytes, Apoptosis Regulatory Proteins, Programmed Cell Death 1 Receptor

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PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection

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