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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3679-3687. Prepublished online as a Blood First Edition Paper on August 26, 2008; DOI 10.1182/blood-2008-01-135442. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-01-135442v1 112/9/3679    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 Lichterfeld, M. Articles by Yu, X. G. Search for Related Content PubMed PubMed Citation Articles by Lichterfeld, M. Articles by Yu, X. G. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Telomerase activity of HIV-1–specific CD8+ T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors Mathias Lichterfeld1,2,*, Danlei Mou1,*, Thai Duong Hong Cung1, Katie L. Williams1, Michael T. Waring1,3, Jinghe Huang1, Florencia Pereyra1, Alicja Trocha1, Gordon J. Freeman4, Eric S. Rosenberg1,2, Bruce D. Walker1,3, and Xu G. Yu1 1 Partners AIDS Research Center and Harvard University Center for AIDS Research, and 2 Division of Infectious Diseases, Massachusetts General Hospital, Boston; 3 Howard Hughes Medical Institute, Chevy Chase, MD; and 4 Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA Exhaustion of virus-specific T cells may play an important role in the pathophysiology of chronic viral infections. Here, we analyzed telomere length and telomerase activity in HIV-1–specific CD8+ T cells from progressors or controllers to determine underlying molecular pathways of T-cell exhaustion and senescence. Telomere lengths of HIV-1–specific CD8+ T cells from progressors were significantly shorter compared with autologous cytomegalovirus (CMV)/Epstein-Barr virus (EBV)–specific CD8+ T cells or bulk CD8+ T cells, while telomere lengths from controllers significantly exceeded those of autologous bulk CD8+ T cells and reached a similar level as HIV-1–specific CD8+ T cells collected during primary HIV-1 infection. Telomere length stabilization in controllers corresponded to high levels of constitutive telomerase activity, which was associated with preservation of cytotoxic and proliferative properties. Conversely, limited constitutive telomerase activity was observed in HIV-1–specific CD8+ T cells from progressors, although an increase in both telomere length and telomerase activity was achieved in antigenic-peptide–stimulated cells from progressors after blocking the PD-1/PD ligand 1 (PD-L1) pathway. Collectively, these data suggest a causal role of telomere shortening for the functional deficiencies of HIV-1–specific CD8+ T cells in chronic progressive infection, while high constitutive telomerase activities appears to contribute to maintenance of polyfunctional HIV-1–specific CD8+ T cells from HIV-1 controllers. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. M. Henson, O. Franzese, R. Macaulay, V. Libri, R. I. Azevedo, S. Kiani-Alikhan, F. J. Plunkett, J. E. Masters, S. Jackson, S. J. Griffiths, et al. KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cells Blood, June 25, 2009; 113(26): 6619 - 6628. [Abstract] [Full Text] [PDF] J. R. Almeida, D. Sauce, D. A. Price, L. Papagno, S. Y. Shin, A. Moris, M. Larsen, G. Pancino, D. C. Douek, B. Autran, et al. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity Blood, June 18, 2009; 113(25): 6351 - 6360. [Abstract] [Full Text] [PDF] A. Saez-Cirion, M. Sinet, S. Y. Shin, A. Urrutia, P. Versmisse, C. Lacabaratz, F. Boufassa, V. Avettand-Fenoel, C. Rouzioux, J.-F. Delfraissy, et al. Heterogeneity in HIV Suppression by CD8 T Cells from HIV Controllers: Association with Gag-Specific CD8 T Cell Responses J. Immunol., June 15, 2009; 182(12): 7828 - 7837. [Abstract] [Full Text] [PDF] D. E. Kaufmann and B. D. Walker PD-1 and CTLA-4 Inhibitory Cosignaling Pathways in HIV Infection and the Potential for Therapeutic Intervention J. Immunol., May 15, 2009; 182(10): 5891 - 5897. [Abstract] [Full Text] [PDF]

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