PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Abstract
Functional impairment of T cells is characteristic of many chronic mouse and human viral infections. The inhibitory receptor programmed death 1 (PD-1; also known as PDCD1), a negative regulator of activated T cells, is markedly upregulated on the surface of exhausted virus-specific CD8 T cells in mice. Blockade of this pathway using antibodies against the PD ligand 1 (PD-L1, also known as CD274) restores CD8 T-cell function and reduces viral load. To investigate the role of PD-1 in a chronic human viral infection, we examined PD-1 expression on human immunodeficiency virus (HIV)-specific CD8 T cells in 71 clade-C-infected people who were naive to anti-HIV treatments, using ten major histocompatibility complex (MHC) class I tetramers specific for frequently targeted epitopes. Here we report that PD-1 is significantly upregulated on these cells, and expression correlates with impaired HIV-specific CD8 T-cell function as well as predictors of disease progression: positively with plasma viral load and inversely with CD4 T-cell count. PD-1 expression on CD4 T cells likewise showed a positive correlation with viral load and an inverse correlation with CD4 T-cell count, and blockade of the pathway augmented HIV-specific CD4 and CD8 T-cell function. These data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function. Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection.
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Exhausted T cells can occur in cancer, not only in chronic viral infections.
“Originally described in the context of chronic viral infections, where the host fails to clear the pathogen, it is now apparent that exhausted T cells can also occur in cancer (12, 13).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [12]
Cites
Phenotypic Analysis of Antigen-Specific T Lymphocytes
Altman, J. D., Moss, P. A. H., Goulder, P. J. R., Barouch, D. H., McHeyzer-Williams, M. G., Bell, J. I., McMichael, A. J., & Davis, M. M. (1996) · Science · doi:10.1126/science.274.5284.94 · Cited by 3,544 · see citing works
Self-citation
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Cited by
Sorted by citations
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Herbst, R. S., Soria, J.-C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., Sosman, J. A., McDermott, D. F., Powderly, J. D., Gettinger, S. N., et al. (2014) · Nature · doi:10.1038/nature14011 · Cited by 5,231 · see citing works
PD-1 and Its Ligands in Tolerance and Immunity
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
Self-citationMolecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652 · see citing works
Self-citationWherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · see citing works
Self-citationMolecular 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 · see citing works
Self-citationBlackburn, 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
Self-citationTargeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100643 · Cited by 2,072 · see citing works
Ahmadzadeh, M., Johnson, L. A., Heemskerk, B., Wunderlich, J. R., Dudley, M. E., White, D. E., & Rosenberg, S. A. (2009) · Blood · doi:10.1182/blood-2008-12-195792 · Cited by 1,766 · see citing works
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689 · see citing works
Inhibitory B7-family molecules in the tumour microenvironment
Zou, W., & Chen, L. (2008) · Nature Reviews Immunology · doi:10.1038/nri2326 · Cited by 1,608 · see citing works
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360 · see citing works
Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378 · see citing works
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 · see citing works
Fourcade, J., Sun, Z., Benallaoua, M., Guillaume, P., Luescher, I. F., Sander, C., Kirkwood, J. M., Kuchroo, V., & Zarour, H. M. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100637 · Cited by 1,307 · see citing works
Thommen, D. S., Koelzer, V. H., Herzig, P., Roller, A., Trefny, M., Dimeloe, S., Kiialainen, A., Hanhart, J., Schill, C., Hess, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0057-z · Cited by 1,161 · see citing works
“5 (2D1), -CD56 PE (CMSSB), - CD3 APC-eFluor780 (SK7), -Lag-3 FITC (3DS223H), -TIGIT PE (MBSA43), -2B4 FITC (eBioDM244), -CD137 FITC (4B4), -IL-2 PE (MQ1-17H12), -TNF-α APC (MAb11), - CD26 FITC (2A6), -CXCR5 Biotin (MU5UBEE), -ICOS FITC (ISA-3), -CD38 APC (HIT2), -Eomes eFluor660 (WD1928), -T-bet PE (eBio4B10), -pSTAT3…”
InfluentialYokosuka, T., Takamatsu, M., Kobayashi-Imanishi, W., Hashimoto-Tane, A., Azuma, M., & Saito, T. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112741 · Cited by 1,161 · see citing works
The immune system’s role in sepsis progression, resolution, and long-term outcome
Delano, M. J., & Ward, P. A. (2016) · Immunological Reviews · doi:10.1111/imr.12499 · Cited by 880 · see citing works
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., Gostick, E., Adams, W. C., Precopio, M. L., Schacker, T., Roederer, M., Douek, D. C., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061496 · Cited by 889 · see citing works
PD-1 signaling in primary T cells
Riley, J. L. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00767.x · Cited by 778 · see citing works
Blockade of chronic type I interferon signaling to control persistent LCMV infection
Wilson, E. B., Yamada, D. H., Elsaesser, H., Herskovitz, J., Deng, J., Cheng, G., Aronow, B. J., Karp, C. L., & Brooks, D. G. (2013) · Science · doi:10.1126/science.1235208 · Cited by 709 · see citing works
Zhou, Q., Munger, M. E., Veenstra, R. G., Weigel, B. J., Hirashima, M., Munn, D. H., Murphy, W. J., Azuma, M., Anderson, A. C., Kuchroo, V. K., et al. (2011) · Blood · doi:10.1182/blood-2010-10-310425 · Cited by 675 · see citing works
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622 · see citing works
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
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
Dustin, M. L. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0161 · Cited by 502 · see citing works
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
Self-citationReversing T-cell Dysfunction and Exhaustion in Cancer
Zarour, H. M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1849 · Cited by 462 · 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
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
Inman, B. A., Sebo, T. J., Frigola, X., Dong, H., Bergstralh, E. J., Frank, I., Fradet, Y., Lacombe, L., & Kwon, E. D. (2007) · Cancer · doi:10.1002/cncr.22588 · Cited by 438 · see citing works
PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines
Peng, W., Liu, C., Xu, C., Lou, Y., Chen, J., Yang, Y., Yagita, H., Overwijk, W. W., Lizée, G., Radvanyi, L., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1187 · Cited by 432 · 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
Self-citationBaessler, 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
Wu, K., Kryczek, I., Chen, L., Zou, W., & Welling, T. H. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-0901 · Cited by 380 · see citing works
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-citationFrom “truly naïve” to “exhausted senescent” T cells: When markers predict functionality
Larbi, A., & Fulop, T. (2014) · Cytometry Part A · doi:10.1002/cyto.a.22351 · Cited by 359 · see citing works
Tumour burden and efficacy of immune-checkpoint inhibitors
Dall’Olio, F. G., Marabelle, A., Caramella, C., Garcia, C., Aldea, M., Chaput, N., Robert, C., & Besse, B. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00564-3 · Cited by 350 · see citing works
Immune checkpoint inhibitors in challenging populations
Johnson, D. B., Sullivan, R. J., & Menzies, A. M. (2017) · Cancer · doi:10.1002/cncr.30642 · Cited by 339 · see citing works
Verma, V., Shrimali, R. K., Ahmad, S., Dai, W., Wang, H., Lu, S., Nandre, R., Gaur, P., Lopez, J., Sade-Feldman, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0441-y · Cited by 333 · see citing works
Chew, G. M., Fujita, T., Webb, G. M., Burwitz, B. J., Wu, H. L., Reed, J. S., Hammond, K. B., Clayton, K. L., Ishii, N., Abdel-Mohsen, M., et al. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005349 · Cited by 323 · see citing works
The size of the viral inoculum contributes to the outcome of hepatitis B virus infection
Asabe, S., Wieland, S. F., Chattopadhyay, P. K., Roederer, M., Engle, R. E., Purcell, R. H., & Chisari, F. V. (2009) · Journal of Virology · doi:10.1128/jvi.00867-09 · Cited by 320 · see citing works
Phosphotyrosine-Dependent Coupling of Tim-3 to T-Cell Receptor Signaling Pathways
Lee, J., Su, E. W., Zhu, C., Hainline, S., Phuah, J., Moroco, J. A., Smithgall, T. E., Kuchroo, V. K., & Kane, L. P. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05297-11 · Cited by 285 · see citing works
TGFβ1-Mediated SMAD3 Enhances PD-1 Expression on Antigen-Specific T Cells in Cancer
Park, B. V., Freeman, Z. T., Ghasemzadeh, A., Chattergoon, M. A., Rutebemberwa, A., Steigner, J., Winter, M. E., Huynh, T. V., Sebald, S. M., Lee, S.-J., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1347 · Cited by 287 · see citing works
Cytomegalovirus Infection: A Driving Force in Human T Cell Immunosenescence
KOCH, S., LARBI, A., ÖZCELIK, D., SOLANA, R., GOUTTEFANGEAS, C., ATTIG, S., WIKBY, A., STRINDHALL, J., FRANCESCHI, C., & PAWELEC, G. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1396.043 · Cited by 242 · see citing works
Plunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., & Akbar, A. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.12.7710 · Cited by 222 · see citing works
The metabolic life and times of a T‐cell
Michalek, R. D., & Rathmell, J. C. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00911.x · Cited by 186 · see citing works
“For example, inhibitory costimulatory receptors, such as programmed death-1 (PD-1), have been shown to suppress T-cell growth and proliferation when chronically stimulated (102, 103).”
BackgroundPD-1 expression on dendritic cells suppresses CD8<sup>+</sup>T cell function and antitumor immunity
Lim, T. S., Chew, V., Sieow, J. L., Goh, S., Yeong, J. P.-S., Soon, A. L., & Ricciardi-Castagnoli, P. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1085146 · Cited by 184 · see citing works
Henson, S. M., Macaulay, R., Riddell, N. E., Nunn, C. J., & Akbar, A. N. (2015) · European Journal of Immunology · doi:10.1002/eji.201445312 · Cited by 146 · see citing works
de Coaña, Y. P., Wolodarski, M., Poschke, I., Yoshimoto, Y., Yang, Y., Nyström, M., Edbäck, U., Brage, S. E., Lundqvist, A., Masucci, G. V., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15368 · Cited by 139 · see citing works
Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs
Gupta, S., Thornley, T. B., Gao, W., Larocca, R., Turka, L. A., Kuchroo, V. K., & Strom, T. B. (2012) · Journal of Clinical Investigation · doi:10.1172/jci45138 · Cited by 139 · see citing works
Wang, J., DeClercq, J. J., Hayward, S. B., Li, P. W.-L., Shivak, D. A., Gregory, P. D., Lee, G., & Holmes, M. C. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkv1121 · Cited by 128 · see citing works
Targeting the immune microenvironment in acute myeloid leukemia: a focus on T cell immunity
Lamble, A. J., & Lind, E. F. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00213 · Cited by 119 · see citing works
Telomerase in T Lymphocytes: Use It and Lose It?
Akbar, A. N., & Vukmanovic-Stejic, M. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.11.6689 · Cited by 96 · see citing works
Lin, S.-W., Hensley, S. E., Tatsis, N., Lasaro, M. O., & Ertl, H. C. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci33138 · Cited by 88 · see citing works
Clonal lineage tracing reveals mechanisms skewing CD8+ T cell fate decisions in chronic infection
Kasmani, M. Y., Zander, R., Chung, H. K., Chen, Y., Khatun, A., Damo, M., Topchyan, P., Johnson, K. E., Levashova, D., Burns, R., et al. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20220679 · Cited by 87 · see citing works
Li, H., Lasaro, M. O., Jia, B., Lin, S. W., Haut, L. H., High, K. A., & Ertl, H. C. (2011) · Molecular Therapy · doi:10.1038/mt.2011.81 · Cited by 83 · see citing works
PD-1 coinhibitory signals: the link between pathogenesis and protection
Kulpa, D. A., Lawani, M., Cooper, A., Peretz, Y., Ahlers, J., & Sékaly, R.-P. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.02.002 · Cited by 70 · see citing works
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 · see citing works
Self-citationDUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia
Bignon, A., Régent, A., Klipfel, L., Desnoyer, A., de la Grange, P., Martinez, V., Lortholary, O., Dalloul, A., Mouthon, L., & Balabanian, K. (2015) · Blood · doi:10.1182/blood-2014-08-598565 · Cited by 51 · see citing works
Lazuardi, L., Herndler-Brandstetter, D., Brunner, S., Laschober, G. T., Lepperdinger, G., & Grubeck-Loebenstein, B. (2009) · Biogerontology · doi:10.1007/s10522-008-9167-1 · Cited by 43 · see citing works
Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockade
Henson, S. M., Macaulay, R., Franzese, O., & Akbar, A. N. (2012) · Immunology · doi:10.1111/j.1365-2567.2011.03550.x · Cited by 42 · see citing works
Yassin, M., Sadowska, Z., Djurhuus, D., Nielsen, B., Tougaard, P., Olsen, J., & Pedersen, A. E. (2019) · Immunology · doi:10.1111/imm.13093 · Cited by 38 · see citing works
Tang, X., Deng, B., Zang, A., He, X., Zhou, Y., Wang, D., Li, D., Dai, X., Chen, J., Zhang, X., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940577 · Cited by 39 · see citing works
Grant, M. J., DeVito, N., & Salama, A. K. S. (2018) · Melanoma Management · doi:10.2217/mmt-2018-0004 · Cited by 24 · see citing works
Ames, R. Y., Ting, L.-M., Gendlina, I., Kim, K., & Macian, F. (2017) · Infection and Immunity · doi:10.1128/iai.00364-17 · Cited by 16 · see citing works
Lichterfeld, M., Cung, T., Seiss, K., Rosenberg, E. S., Pereyra, F., & Yu, X. G. (2012) · Journal of Virology · doi:10.1128/jvi.00196-12 · Cited by 9 · see citing works
- Authors
- 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., Mncube, Z., Duraiswamy, J., Zhu, B., Eichbaum, Q., Altfeld, M., Wherry, E. J., Coovadia, H. M., Goulder, P. J. R., Klenerman, P., Ahmed, R., Freeman, G. J., & Walker, B. D.
- Affiliations
- University of KwaZulu-Natal (ZA)
- Harvard University (US)
- Emory University (US)
- University of Oxford (GB)
- The Wistar Institute (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Walker, Bruce D.
- ORCID
- Venue
- Nature
- Published
- 2006-08-20
- Volume
- 443
- Issue
- 7109
- Pages
- 350-354
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1978436252
- Cited by
- 2,680
- References
- 1
- Citations by year
- 2026: 54 · 2025: 84 · 2024: 95 · 2023: 91 · 2022: 119 · 2021: 164 · 2020: 135 · 2019: 127 · 2018: 147 · 2017: 143 · 2016: 140 · 2015: 146 · 2014: 144 · 2013: 151 · 2012: 145
- FWCI
- 53.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- PD-1, PD-L1, HIV-specific CD8+ T cells, T cell exhaustion, chronic HIV infection, disease progression, viral load, CD4 count, anti-PD-1 therapy, immune regulation, MHC class I tetramers
- MeSH terms
- HIV, Humans, Interferon-gamma, Histocompatibility Antigens Class I, CD4-Positive T-Lymphocytes, HIV Infections, Antigens, CD, Up-Regulation, Gene Expression, CD8-Positive T-Lymphocytes, Disease Progression, Apoptosis Regulatory Proteins, Programmed Cell Death 1 Receptor
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