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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 451694, 9 pages
http://dx.doi.org/10.1155/2011/451694
Review Article

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.

Linked References

  1. 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. View at Publisher · View at Google Scholar · View at Scopus
  2. 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. View at Scopus
  3. 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. View at Scopus
  4. 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. View at Publisher · View at Google Scholar · View at Scopus
  5. 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. View at Publisher · View at Google Scholar · View at Scopus
  6. 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. View at Scopus
  7. 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 CD8+ T cell responses during chronic infection,” Nature Immunology, vol. 12, no. 7, pp. 663–671, 2011. View at Publisher · View at Google Scholar
  8. 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. View at Publisher · View at Google Scholar · View at Scopus
  9. 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. View at Publisher · View at Google Scholar · View at Scopus
  10. 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. View at Publisher · View at Google Scholar · View at Scopus
  11. L. L. Carter, L. A. Fouser, J. Jussif et al., “PD-1:PD-L inhibitory pathway affects both CD4+ and CD4+ T cells and is overcome by IL-2,” European Journal of Immunology, vol. 32, no. 3, pp. 634–643, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. 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. View at Scopus
  13. 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. View at Publisher · View at Google Scholar · View at Scopus
  14. 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. View at Publisher · View at Google Scholar · View at Scopus
  15. 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. View at Scopus
  16. 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. View at Publisher · View at Google Scholar · View at Scopus
  17. 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. View at Scopus
  18. 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. View at Publisher · View at Google Scholar · View at Scopus
  19. 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. View at Publisher · View at Google Scholar · View at Scopus
  20. 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. View at Publisher · View at Google Scholar · View at Scopus
  21. 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. View at Publisher · View at Google Scholar · View at Scopus
  22. 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. View at Publisher · View at Google Scholar · View at Scopus
  23. 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. View at Publisher · View at Google Scholar · View at Scopus
  24. 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. View at Publisher · View at Google Scholar · View at Scopus
  25. 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. View at Publisher · View at Google Scholar · View at Scopus
  26. 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. View at Publisher · View at Google Scholar · View at Scopus
  27. 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. View at Publisher · View at Google Scholar · View at Scopus
  28. E. J. Wherry, S. J. Ha, S. M. Kaech et al., “Molecular signature of CD8+ T cell exhaustion during chronic viral infection,” Immunity, vol. 27, no. 4, pp. 670–684, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. 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. View at Publisher · View at Google Scholar · View at Scopus
  30. 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. View at Publisher · View at Google Scholar · View at Scopus
  31. 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. View at Publisher · View at Google Scholar · View at Scopus
  32. 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/.
  33. 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. View at Publisher · View at Google Scholar · View at Scopus
  34. L. Trautmann, L. Janbazian, N. Chomont et al., “Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction,” Nature Medicine, vol. 12, no. 10, pp. 1198–1202, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Y. Zhang, Z. Zhang, X. Wang et al., “PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors,” Blood, vol. 109, no. 11, pp. 4671–4678, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Quigley, F. Pereyra, B. Nilsson et al., “Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF,” Nature Medicine, vol. 16, no. 10, pp. 1147–1151, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. 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. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Petrovas, D. A. Price, J. Mattapallil et al., “SIV-specific CD8+ 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. View at Publisher · View at Google Scholar · View at Scopus
  39. M. D'Souza, A. P. Fontenot, D. G. Mack et al., “Programmed death 1 expression on HIV-specific CD4+ 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. View at Scopus
  40. E. A. Said, F. P. Dupuy, L. Trautmann et al., “Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection,” Nature Medicine, vol. 16, no. 4, pp. 452–459, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. 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. View at Publisher · View at Google Scholar · View at Scopus
  42. 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. View at Publisher · View at Google Scholar · View at Scopus
  43. 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. View at Publisher · View at Google Scholar
  44. 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. View at Publisher · View at Google Scholar · View at Scopus
  45. 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. View at Publisher · View at Google Scholar · View at Scopus
  46. 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. View at Publisher · View at Google Scholar · View at Scopus
  47. 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. View at Publisher · View at Google Scholar · View at Scopus
  48. 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. View at Publisher · View at Google Scholar · View at Scopus
  49. 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. View at Publisher · View at Google Scholar · View at Scopus
  50. 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. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Maier, M. Isogawa, G. J. Freeman, and F. V. Chisari, “PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver,” The Journal of Immunology, vol. 178, no. 5, pp. 2714–2720, 2007. View at Scopus
  52. 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 CD8+ T cells associated with reversible immune dysfunction,” Journal of Virology, vol. 81, no. 17, pp. 9249–9258, 2007. View at Publisher · View at Google Scholar · View at Scopus
  53. 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. View at Publisher · View at Google Scholar · View at Scopus
  54. 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 CD8+ T cells in trigeminal ganglia of latently infected mice,” Journal of Virology, vol. 83, no. 5, pp. 2246–2254, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. 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. View at Publisher · View at Google Scholar · View at Scopus
  56. S. J. Allen, P. Hamrah, D. Gate et al., “The role of LAT in increased CD8+ 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. View at Publisher · View at Google Scholar
  57. 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 CD8+ T cell exhaustion and promotes maintenance of herpes simplex virus 1 latency,” The Journal of Immunology, vol. 184, no. 1, pp. 277–286, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Takamura, S. Tsuji-Kawahara, H. Yagita et al., “Premature terminal exhaustion of friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors,” The Journal of Immunology, vol. 184, no. 9, pp. 4696–4707, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. 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. View at Scopus
  60. 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. View at Publisher · View at Google Scholar · View at Scopus
  61. Y.-Y. Wu, J.-H. Chen, J.-T. Kao et al., “Expression of CD25high regulatory T cells and PD-1 in gastric infiltrating CD8+ T lymphocytes in patients with Helicobacter pylori infection,” Clinical and Vaccine Immunology, vol. 18, no. 7, pp. 1198–1201, 2011. View at Publisher · View at Google Scholar
  62. 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. View at Publisher · View at Google Scholar · View at Scopus
  63. T. Joshi, S. Rodriguez, V. Perovic, I. A. Cockburn, and S. Stäger, “B7-H1 blockade increases survival of dysfunctional CD8+ T cells and confers protection against Leishmania donovaniinfections,” PLoS Pathogens, vol. 5, no. 5, Article ID e1000431, 2009. View at Publisher · View at Google Scholar
  64. R. Bhadra, J. P. Gigley, L. M. Weiss, and I. A. Khan, “Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ 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. View at Publisher · View at Google Scholar
  65. 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. View at Scopus
  66. D. G. Colley, L. E. Sasser, and A. M. Reed, “PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity,” Parasite Immunology, vol. 27, no. 1-2, pp. 45–53, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. 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. View at Publisher · View at Google Scholar · View at Scopus
  68. 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. View at Scopus
  69. M. -Y. Song, S. -H. Park, H. J. Nam, D. -H. Choi, and Y. -C. Sung, “Enhancement of vaccine-induced primary and memory CD8+ t-cell responses by soluble PD-1,” The Journal of Immunotherapy, vol. 34, no. 3, pp. 297–306, 2011. View at Publisher · View at Google Scholar
  70. 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. View at Publisher · View at Google Scholar · View at Scopus
  71. 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. View at Publisher · View at Google Scholar · View at Scopus
  72. 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. View at Publisher · View at Google Scholar · View at Scopus
  73. 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. View at Publisher · View at Google Scholar · View at Scopus
  74. D. Franceschini, M. Paroli, V. Francavilla et al., “PD-L1 negatively regulates CD4+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. View at Publisher · View at Google Scholar · View at Scopus
  75. 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. View at Publisher · View at Google Scholar · View at Scopus
  76. 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. View at Publisher · View at Google Scholar · View at Scopus
  77. 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. View at Publisher · View at Google Scholar · View at Scopus
  78. 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. View at Publisher · View at Google Scholar · View at Scopus
  79. 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. View at Publisher · View at Google Scholar