|
|
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.
 Previous Article | Next Article 
Submitted January 24, 2008
Accepted August 4, 2008
Telomerase activity of HIV-1-specific CD8+ T cells: Constitutive upregulation in controllers and selective increase by blockade of PD ligand 1 in progressors
Mathias Lichterfeld, Danlei Mou, Thai Duong Hong Cung, Katie L. Williams, Michael T. Waring, Jinghe Huang, Florencia Pereyra, Alicja Trocha, Gordon J. Freeman, Eric S. Rosenberg, Bruce D. Walker, and Xu G. Yu*
Partners AIDS Research Center, Massachusetts General Hospital, Boston, MA, United States
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Howard Hughes Medical Institute, Chevy Chase, MD, United States
* Corresponding author; email: xyu{at}partners.org.
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 to autologous CMV-/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-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]
|
|
|
|
|
