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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 451694, 9 pages
The PD-1/PD-L1 (B7-H1) Pathway in Chronic Infection-Induced Cytotoxic T Lymphocyte Exhaustion
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
3Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
4Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
5Einstein-Montefiore Center for AIDS Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Received 1 July 2011; Accepted 21 July 2011
Academic Editor: Julie Curtsinger
Copyright © 2011 Kimberly A. Hofmeyer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- X. Zang and J. P. Allison, “The B7 family and cancer therapy: costimulation and coinhibition,” Clinical Cancer Research, vol. 13, no. 18, part 1, pp. 5271–5279, 2007.
- Y. Ishida, Y. Agata, K. Shibahara, and T. Honjo, “Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death,” The EMBO Journal, vol. 11, no. 11, pp. 3887–3895, 1992.
- Y. Agata, A. Kawasaki, H. Nishimura et al., “Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes,” International Immunology, vol. 8, no. 5, pp. 765–772, 1996.
- R. Vibhakar, G. Juan, F. Traganos, Z. Darzynkiewicz, and L. R. Finger, “Activation-induced expression of human programmed death-1 gene in T- lymphocytes,” Experimental Cell Research, vol. 232, no. 1, pp. 25–28, 1997.
- G. J. Freeman, A. J. Long, Y. Iwai et al., “Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation,” The Journal of Experimental Medicine, vol. 192, no. 7, pp. 1027–1034, 2000.
- K. J. Oestreich, H. Yoon, R. Ahmed, and J. M. Boss, “NFATc1 regulates PD-1 expression upon T cell activation,” The Journal of Immunology, vol. 181, no. 7, pp. 4832–4839, 2008.
- C. Kao, K. J. Oestreich, M. A. Paley et al., “Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific T cell responses during chronic infection,” Nature Immunology, vol. 12, no. 7, pp. 663–671, 2011.
- H. Dong, G. Zhu, K. Tamada, and L. Chen, “B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion,” Nature Medicine, vol. 5, no. 12, pp. 1365–1369, 1999.
- Y. Latchman, C. R. Wood, T. Chernova et al., “PD-L2 is a second ligand for PD-1 and inhibits T cell activation,” Nature Immunology, vol. 2, no. 3, pp. 261–268, 2001.
- S. Y. Tseng, M. Otsuji, K. Gorski et al., “B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells,” The Journal of Experimental Medicine, vol. 193, no. 7, pp. 839–845, 2001.
- L. L. Carter, L. A. Fouser, J. Jussif et al., “PD-1:PD-L inhibitory pathway affects both and T cells and is overcome by IL-2,” European Journal of Immunology, vol. 32, no. 3, pp. 634–643, 2002.
- T. Yamazaki, H. Akiba, H. Iwai et al., “Expression of programmed death 1 ligands by murine T cells and APC,” The Journal of Immunology, vol. 169, no. 10, pp. 5538–5545, 2002.
- S. J. Lee, B. C. Jang, S. W. Lee et al., “Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-γ-induced upregulation of B7-H1 (CD274),” FEBS Letters, vol. 580, no. 3, pp. 755–762, 2006.
- P. Loke and J. P. Allison, “PD-L1 and PD-L2 are differentially regulated by Th1 and Th2 cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 9, pp. 5336–5341, 2003.
- J. A. Brown, D. M. Dorfman, F. R. Ma et al., “Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production,” The Journal of Immunology, vol. 170, no. 3, pp. 1257–1266, 2003.
- T. Okazaki, A. Maeda, H. Nishimura, T. Kurosaki, and T. Honjo, “PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 24, pp. 13866–13871, 2001.
- J. M. Chemnitz, R. V. Parry, K. E. Nichols, C. H. June, and J. L. Riley, “SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation,” The Journal of Immunology, vol. 173, no. 2, pp. 945–954, 2004.
- K. A. Sheppard, L. J. Fitz, J. M. Lee et al., “PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ,” FEBS Letters, vol. 574, no. 1-3, pp. 37–41, 2004.
- R. V. Parry, J. M. Chemnitz, K. A. Frauwirth et al., “CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms,” Molecular and Cellular Biology, vol. 25, no. 21, pp. 9543–9553, 2005.
- M. J. Butte, M. E. Keir, T. B. Phamduy, A. H. Sharpe, and G. J. Freeman, “Programmed Death-1 Ligand 1 Interacts Specifically with the B7-1 Costimulatory Molecule to Inhibit T Cell Responses,” Immunity, vol. 27, no. 1, pp. 111–122, 2007.
- H. Nishimura, M. Nose, H. Hiai, N. Minato, and T. Honjo, “Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor,” Immunity, vol. 11, no. 2, pp. 141–151, 1999.
- H. Nishimura, T. Okazaki, Y. Tanaka et al., “Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice,” Science, vol. 291, no. 5502, pp. 319–322, 2001.
- Y. Iwai, S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo, “PD-1 inhibits antiviral immunity at the effector phase in the liver,” The Journal of Experimental Medicine, vol. 198, no. 1, pp. 39–50, 2003.
- B. T. Fife, K. E. Pauken, T. N. Eagar et al., “Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal,” Nature Immunology, vol. 10, no. 11, pp. 1185–1192, 2009.
- L. M. Francisco, V. H. Salinas, K. E. Brown et al., “PD-L1 regulates the development, maintenance, and function of induced regulatory T cells,” The Journal of Experimental Medicine, vol. 206, no. 13, pp. 3015–3029, 2009.
- A. J. Zajac, J. N. Blattman, K. Murali-Krishna et al., “Viral immune evasion due to persistence of activated T cells without effector function,” The Journal of Experimental Medicine, vol. 188, no. 12, pp. 2205–2213, 1998.
- A. Gallimore, A. Glithero, A. Godkin et al., “Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes,” The Journal of Experimental Medicine, vol. 187, no. 9, pp. 1383–1393, 1998.
- E. J. Wherry, S. J. Ha, S. M. Kaech et al., “Molecular signature of T cell exhaustion during chronic viral infection,” Immunity, vol. 27, no. 4, pp. 670–684, 2007.
- D. L. Barber, E. J. Wherry, D. Masopust et al., “Restoring function in exhausted CD8 T cells during chronic viral infection,” Nature, vol. 439, no. 7077, pp. 682–687, 2006.
- J. N. Blattman, E. J. Wherry, S. J. Ha, R. G. Van Der Most, and R. Ahmed, “Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection,” Journal of Virology, vol. 83, no. 9, pp. 4386–4394, 2009.
- S. D. Blackburn, H. Shin, G. J. Freeman, and E. J. Wherry, “Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 39, pp. 15016–15021, 2008.
- UN Joint Programme on HIV/AIDS, Global Report: UNAIDS Report on the Global AIDS Epidemic, December 2010, http://www.unhcr.org/refworld/docid/4cfca9c62.html/.
- C. L. Day, D. E. Kaufmann, P. Kiepiela et al., “PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression,” Nature, vol. 443, no. 7109, pp. 350–354, 2006.
- L. Trautmann, L. Janbazian, N. Chomont et al., “Upregulation of PD-1 expression on HIV-specific T cells leads to reversible immune dysfunction,” Nature Medicine, vol. 12, no. 10, pp. 1198–1202, 2006.
- J. Y. Zhang, Z. Zhang, X. Wang et al., “PD-1 up-regulation is correlated with HIV-specific memory T-cell exhaustion in typical progressors but not in long-term nonprogressors,” Blood, vol. 109, no. 11, pp. 4671–4678, 2007.
- M. Quigley, F. Pereyra, B. Nilsson et al., “Transcriptional analysis of HIV-specific T cells shows that PD-1 inhibits T cell function by upregulating BATF,” Nature Medicine, vol. 16, no. 10, pp. 1147–1151, 2010.
- V. Velu, S. Kannanganat, C. Ibegbu et al., “Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination,” Journal of Virology, vol. 81, no. 11, pp. 5819–5828, 2007.
- C. Petrovas, D. A. Price, J. Mattapallil et al., “SIV-specific T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection,” Blood, vol. 110, no. 3, pp. 928–936, 2007.
- M. D'Souza, A. P. Fontenot, D. G. Mack et al., “Programmed death 1 expression on HIV-specific T cells is driven by viral replication and associated with T cell dysfunction,” The Journal of Immunology, vol. 179, no. 3, pp. 1979–1987, 2007.
- E. A. Said, F. P. Dupuy, L. Trautmann et al., “Programmed death-1-induced interleukin-10 production by monocytes impairs T cell activation during HIV infection,” Nature Medicine, vol. 16, no. 4, pp. 452–459, 2010.
- D. Trabattoni, M. Saresella, M. Biasin et al., “B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression,” Blood, vol. 101, no. 7, pp. 2514–2520, 2003.
- X. Wang, Z. Zhang, S. Zhang et al., “B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection,” European Journal of Immunology, vol. 38, no. 11, pp. 3226–3236, 2008.
- M. Rodríguez-García, F. Porichis, O. G. de Jong et al., “Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10,” Journal of Leukocyte Biology, vol. 89, no. 4, pp. 507–515, 2011.
- A. E. Mitchell, H. M. Colvin, and R. P. Beasley, “Institute of medicine recommendations for the prevention and control of hepatitis B and C,” Hepatology, vol. 51, no. 3, pp. 729–733, 2010.
- M. Kantzanou, M. Lucas, E. Barnes et al., “Viral escape and T cell exhaustion in hepatitis C virus infection analysed using Class I peptide tetramers,” Immunology Letters, vol. 85, no. 2, pp. 165–171, 2003.
- S. Reignat, G. J. M. Webster, D. Brown et al., “Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection,” The Journal of Experimental Medicine, vol. 195, no. 9, pp. 1089–1101, 2002.
- C. Boni, P. Fisicaro, C. Valdatta et al., “Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection,” Journal of Virology, vol. 81, no. 8, pp. 4215–4225, 2007.
- G. Peng, S. Li, W. Wu, X. Tan, Y. Chen, and Z. Chen, “PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients,” Molecular Immunology, vol. 45, no. 4, pp. 963–970, 2008.
- C. Chen, Q. X. Qu, J. A. Huang et al., “Expression of programmed-death receptor ligands 1 and 2 may contribute to the poor stimulatory potential of murine immature dendritic cells,” Immunobiology, vol. 212, no. 3, pp. 159–165, 2007.
- S. Urbani, B. Amadei, D. Tola et al., “PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion,” Journal of Virology, vol. 80, no. 22, pp. 11398–11403, 2006.
- H. Maier, M. Isogawa, G. J. Freeman, and F. V. Chisari, “PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific T lymphocytes in the liver,” The Journal of Immunology, vol. 178, no. 5, pp. 2714–2720, 2007.
- L. Golden-Mason, B. Palmer, J. Klarquist, J. A. Mengshol, N. Castelblanco, and H. R. Rosen, “Upregulation of PD-1 expression on circulating and intrahepatic hepatitis C virus-specific T cells associated with reversible immune dysfunction,” Journal of Virology, vol. 81, no. 17, pp. 9249–9258, 2007.
- N. Nakamoto, H. Cho, A. Shaked et al., “Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade,” PLoS Pathogens, vol. 5, no. 2, Article ID e1000313, 2009.
- K. R. Mott, C. J. Bresee, S. J. Allen, L. BenMohamed, S. L. Wechsler, and H. Ghiasi, “Level of herpes simplex virus type 1 latency correlates with severity of corneal scarring and exhaustion of T cells in trigeminal ganglia of latently infected mice,” Journal of Virology, vol. 83, no. 5, pp. 2246–2254, 2009.
- S. J. Allen, K. R. Mott, M. Zandian, and H. Ghiasi, “Immunization with different viral antigens alters the pattern of T cell exhaustion and latency in herpes simplex virus type 1-infected mice,” Journal of Virology, vol. 84, no. 23, pp. 12315–12324, 2010.
- S. J. Allen, P. Hamrah, D. Gate et al., “The role of LAT in increased T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1,” Journal of Virology, vol. 85, no. 9, pp. 4184–4197, 2011.
- G. M. Frank, A. J. Lepisto, M. L. Freeman, B. S. Sheridan, T. L. Cherpes, and R. L. Hendricks, “Early CD4+ T cell help prevents partial T cell exhaustion and promotes maintenance of herpes simplex virus 1 latency,” The Journal of Immunology, vol. 184, no. 1, pp. 277–286, 2010.
- S. Takamura, S. Tsuji-Kawahara, H. Yagita et al., “Premature terminal exhaustion of friend virus-specific effector T cells by rapid induction of multiple inhibitory receptors,” The Journal of Immunology, vol. 184, no. 9, pp. 4696–4707, 2010.
- S. Das, G. Suarez, E. J. Beswick, J. C. Sierra, D. Y. Graham, and V. E. Reyes, “Expression of B7-H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection,” The Journal of Immunology, vol. 176, no. 5, pp. 3000–3009, 2006.
- P. Mitchell, C. Germain, P. L. Fiori et al., “Chronic exposure to Helicobacter pylori impairs dendritic cell function and inhibits Th1 development,” Infection and Immunity, vol. 75, no. 2, pp. 810–819, 2007.
- Y.-Y. Wu, J.-H. Chen, J.-T. Kao et al., “Expression of CD25high regulatory T cells and PD-1 in gastric infiltrating T lymphocytes in patients with Helicobacter pylori infection,” Clinical and Vaccine Immunology, vol. 18, no. 7, pp. 1198–1201, 2011.
- H. A. Schreiber, P. D. Hulseberg, J. Lee et al., “Dendritic cells in chronic mycobacterial granulomas restrict local anti-bacterial T cell response in a murine model,” PLoS One, vol. 5, no. 7, Article ID e11453, 2010.
- T. Joshi, S. Rodriguez, V. Perovic, I. A. Cockburn, and S. Stäger, “B7-H1 blockade increases survival of dysfunctional T cells and confers protection against Leishmania donovaniinfections,” PLoS Pathogens, vol. 5, no. 5, Article ID e1000431, 2009.
- R. Bhadra, J. P. Gigley, L. M. Weiss, and I. A. Khan, “Control of Toxoplasma reactivation by rescue of dysfunctional T-cell response via PD-1-PDL-1 blockade,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 22, pp. 9196–9201, 2011.
- P. Smith, C. M. Walsh, N. E. Mangan et al., “Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages,” The Journal of Immunology, vol. 173, no. 2, pp. 1240–1248, 2004.
- D. G. Colley, L. E. Sasser, and A. M. Reed, “PD-L2+ dendritic cells and PD-1+ T cells in schistosomiasis correlate with morbidity,” Parasite Immunology, vol. 27, no. 1-2, pp. 45–53, 2005.
- C. S. Rollier, G. Paranhos-Baccala, E. J. Verschoor et al., “Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity,” Hepatology, vol. 45, no. 3, pp. 602–613, 2007.
- A. C. Finnefrock, A. Tang, F. Li et al., “PD-1 blockade in rhesus macaques: impact on chronic infection and prophylactic vaccination,” The Journal of Immunology, vol. 182, no. 2, pp. 980–987, 2009.
- M. -Y. Song, S. -H. Park, H. J. Nam, D. -H. Choi, and Y. -C. Sung, “Enhancement of vaccine-induced primary and memory t-cell responses by soluble PD-1,” The Journal of Immunotherapy, vol. 34, no. 3, pp. 297–306, 2011.
- S. J. Ha, S. N. Mueller, E. J. Wherry et al., “Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection,” The Journal of Experimental Medicine, vol. 205, no. 3, pp. 543–555, 2008.
- S. N. Mueller, M. Matloubian, D. M. Clemens et al., “Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 39, pp. 15430–15435, 2007.
- V. Velu, K. Titanji, B. Zhu et al., “Enhancing SIV-specific immunity in vivo by PD-1 blockade,” Nature, vol. 458, no. 7235, pp. 206–210, 2009.
- R. Berger, R. Rotem-Yehudar, G. Slama et al., “Phase i safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies,” Clinical Cancer Research, vol. 14, no. 10, pp. 3044–3051, 2008.
- D. Franceschini, M. Paroli, V. Francavilla et al., “PD-L1 negatively regulates CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV,” The Journal of Clinical Investigation, vol. 119, no. 3, pp. 551–564, 2009.
- D. G. Brooks, S. J. Ha, H. Elsaesser, A. H. Sharpe, G. J. Freeman, and M. B. A. Oldstone, “IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 51, pp. 20428–20433, 2008.
- S. D. Blackburn, H. Shin, W. N. Haining et al., “Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection,” Nature Immunology, vol. 10, no. 1, pp. 29–37, 2009.
- K. Titanji, V. Velu, L. Chennareddi et al., “Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques,” The Journal of Clinical Investigation, vol. 120, no. 11, pp. 3878–3890, 2010.
- E. Lázár-Molnár, B. Chen, K. A. Sweeney et al., “Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 30, pp. 13402–13407, 2010.
- D. L. Barber, K. D. Mayer-Barber, C. G. Feng, A. H. Sharpe, and A. Sher, “CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition,” The Journal of Immunology, vol. 186, no. 3, pp. 1598–1607, 2011.