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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4671-4678. Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-09-044826. This Article Full Text (PDF) All Versions of this Article: blood-2006-09-044826v1 109/11/4671    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhang, J.-Y. Articles by Wang, F.-S. Search for Related Content PubMed PubMed Citation Articles by Zhang, J.-Y. Articles by Wang, F.-S. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 1, 2006 Accepted January 29, 2007 PD-1 upregulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors, but not in long-term non-progressors Ji-Yuan Zhang, Zheng Zhang, Xicheng Wang, Jun-Liang Fu, Jinxia Yao, Yanmei Jiao, Liangen Chen, Hui Zhang, Jianan Wei, Lei Jin, Ming Shi, George Fu Gao, Hao Wu, and Fu-Sheng Wang* Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China Research Center of Biological Therapy, Beijing, China Department of Infectious Diseases, Beijing You-An Hospital Affiliated to Capital University of Medical Science, Beijing, China HIV/AIDS Research Center, Beijing Guang-An-Men Hospital, Beijing, China * Corresponding author; email: fswang{at}public.bta.net.cn. The immunoreceptor PD-1 is significantly upregulated on exhausted CD8+ T cells during chronic viral infections like HIV-1. However, it remains unknown whether PD-1 expression on CD8+ T cells differs between typical progressors (TP) and long-term non-progressors (LTNP). In this report, we examined PD-1 expression on HIV-specific CD8+ T cells from 63 adults with chronic HIV infection. We found that LTNP exhibited functional HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TP, in contrast, showed significantly up-regulated PD-1 expression that was closely correlated with a reduction in CD4 T-cell number and an elevation in plasma viral load. Importantly, PD-1 upregulation was also associated with reduced perforin and IFN- production, as well as decreased HIV-specific effector memory CD8+ T-cell proliferation in TP but not LTNP individuals. Blocking PD-1/PD-L1 interactions efficiently restored HIV-specific CD8+ T-cell effector function and proliferation. Taken together, these findings confirm the hypothesis that high PD-1 upregulation mediates HIV-specific CD8+ T-cell exhaustion. Blocking PD-1/PD-L1 pathway may represent a new therapeutic option for this disease, and provide more insight into immune pathogenesis in LTNP individuals. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PD-1+ T cells: exhausted and premature? Lishan Su Blood 2007 109: 4593-4594. [Full Text] [PDF] This article has been cited by other articles: R. C. Zahn, M. D. Rett, B. Korioth-Schmitz, Y. Sun, A. P. Buzby, S. Goldstein, C. R. Brown, R. A. Byrum, G. J. Freeman, N. L. Letvin, et al. Simian Immunodeficiency Virus (SIV)-Specific CD8+ T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm J. Virol., December 1, 2008; 82(23): 11577 - 11588. [Abstract] [Full Text] [PDF] D. A. Hafler and V. Kuchroo TIMs: central regulators of immune responses J. Exp. 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Silvestri, and A. T. Haase Early Resolution of Acute Immune Activation and Induction of PD-1 in SIV-Infected Sooty Mangabeys Distinguishes Nonpathogenic from Pathogenic Infection in Rhesus Macaques J. Immunol., May 15, 2008; 180(10): 6798 - 6807. [Abstract] [Full Text] [PDF] E. R. Van Gulck, G. Vanham, L. Heyndrickx, S. Coppens, K. Vereecken, D. Atkinson, E. Florence, I. Kint, Z. N. Berneman, and V. V. Tendeloo Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by gag mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals J. Virol., April 1, 2008; 82(7): 3561 - 3573. [Abstract] [Full Text] [PDF] S.-J. Ha, S. N. Mueller, E. J. Wherry, D. L. Barber, R. D. Aubert, A. H. Sharpe, G. J. Freeman, and R. Ahmed Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection J. Exp. Med., March 17, 2008; 205(3): 543 - 555. [Abstract] [Full Text] [PDF] V. Kasprowicz, J. Schulze zur Wiesch, T. Kuntzen, B. E. Nolan, S. Longworth, A. Berical, J. Blum, C. McMahon, L. L. Reyor, N. Elias, et al. High Level of PD-1 Expression on Hepatitis C Virus (HCV)-Specific CD8+ and CD4+ T Cells during Acute HCV Infection, Irrespective of Clinical Outcome J. Virol., March 15, 2008; 82(6): 3154 - 3160. [Abstract] [Full Text] [PDF] T. Yoshida, F. Jiang, T. Honjo, and T. Okazaki PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice PNAS, March 4, 2008; 105(9): 3533 - 3538. [Abstract] [Full Text] [PDF] K. L. Alderson, Q. Zhou, V. Berner, D. E. C. Wilkins, J. M. Weiss, B. R. Blazar, L. A. Welniak, R. H. Wiltrout, D. Redelman, and W. J. Murphy Regulatory and Conventional CD4+ T Cells Show Differential Effects Correlating with PD-1 and B7-H1 Expression after Immunotherapy J. Immunol., March 1, 2008; 180(5): 2981 - 2988. [Abstract] [Full Text] [PDF] B. E. Palmer, D. G. Mack, A. K. Martin, M. Gillespie, M. M. Mroz, L. A. Maier, and A. P. Fontenot Up-Regulation of Programmed Death-1 Expression on Beryllium-Specific CD4+ T Cells in Chronic Beryllium Disease J. Immunol., February 15, 2008; 180(4): 2704 - 2712. [Abstract] [Full Text] [PDF] C. Wang, T. Wen, J.-P. Routy, N. F. Bernard, R. P. Sekaly, and T. H. Watts 4-1BBL Induces TNF Receptor-Associated Factor 1-Dependent Bim Modulation in Human T Cells and Is a Critical Component in the Costimulation-Dependent Rescue of Functionally Impaired HIV-Specific CD8 T Cells J. Immunol., December 15, 2007; 179(12): 8252 - 8263. [Abstract] [Full Text] [PDF]

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