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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 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 Citation Map 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 Immunobiology Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors Ji-Yuan Zhang1,2, Zheng Zhang2, Xicheng Wang3, Jun-Liang Fu2, Jinxia Yao2, Yanmei Jiao3, Liangen Chen2, Hui Zhang2, Jianan Wei4, Lei Jin2, Ming Shi2, George Fu Gao1, Hao Wu3, and Fu-Sheng Wang1,2 1 Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; 2 Research Center of Biological Therapy, Beijing 302 Hospital, Beijing, China; 3 Department of Infectious Diseases, Beijing You-an Hospital Affiliated with Capital University of Medical Science, Beijing, China; 4 HIV/AIDS Research Center, Beijing Guang-An-Men Hospital, Beijing, China The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8+ T cells during chronic viral infections such as HIV-1. However, it remains unknown whether PD-1 expression on CD8+ T cells differs between typical progressors (TPs) and long-term nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8+ T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TPs, 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 up-regulation was also associated with reduced perforin and IFN- production, as well as decreased HIV-specific effector memory CD8+ T-cell proliferation in TPs but not LTNPs. 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 up-regulation mediates HIV-specific CD8+ T-cell exhaustion. Blocking the PD-1/PD-L1 pathway may represent a new therapeutic option for this disease and provide more insight into immune pathogenesis in LTNPs. 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. Med., November 24, 2008; 205(12): 2699 - 2701. [Abstract] [Full Text] [PDF] S. D. Blackburn, H. Shin, G. J. Freeman, and E. J. 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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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