This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Alter, G.
Right arrow Articles by Altfeld, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alter, G.
Right arrow Articles by Altfeld, M.

 Previous Article  |  Next Article 

Journal of Virology, October 2008, p. 9668-9677, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00341-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Ligand-Independent Exhaustion of Killer Immunoglobulin-Like Receptor-Positive CD8+ T Cells in Human Immunodeficiency Virus Type 1 Infection{triangledown}

Galit Alter,* Suzannah Rihn, Hendrik Streeck, Nickolas Teigen, Alicja Piechocka-Trocha, Kristin Moss, Kristen Cohen, Angela Meier, Florencia Pereyra, Bruce Walker, and Marcus Altfeld

Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts

Received 16 February 2008/ Accepted 19 June 2008

Virus-specific CD8+ T cells play a central role in the control of viral infections, including human immunodeficiency virus type 1 (HIV-1) infection. However, despite the presence of strong and broad HIV-specific CD8+ T-cell responses in chronic HIV-1 infection, these cells progressively lose critical effector functions and fail to clear the infection. Mounting evidence suggests that the upregulation of several inhibitory regulatory receptors on the surface of CD8+ T cells during HIV-1 infection may contribute directly to the impairment of T-cell function. Here, we investigated the role of killer immunoglobulin receptors (KIR), which are expressed on NK cells and on CD8+ T cells, in regulating CD8+ T-cell function in HIV-1 infection. KIR expression was progressively upregulated on CD8+ T cells during HIV-1 infection and correlated with the level of viral replication. Expression of KIR was associated with a profound inhibition of cytokine secretion, degranulation, proliferation, and activation by CD8+ T cells following stimulation with T-cell receptor (TCR)-dependent stimuli. In contrast, KIR+ CD8+ T cells responded potently to TCR-independent stimulation, demonstrating that these cells are functionally competent. KIR-associated suppression of CD8+ T-cell function was independent of ligand engagement, suggesting that these regulatory receptors may constitutively repress TCR activation. This ligand-independent repression of TCR activation of KIR+ CD8+ T cells may represent a significant barrier to therapeutic interventions aimed at improving the quality of the HIV-specific CD8+ T-cell response in infected individuals.

* Corresponding author. Mailing address: Partners AIDS Research Center, Massachusetts General Hospital, 149 13th Street, Boston, MA 02129. Phone: (617) 724-0546. Fax: (617) 726-5411. E-mail: galter{at}partners.org

{triangledown} Published ahead of print on 25 June 2008.

Journal of Virology, October 2008, p. 9668-9677, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00341-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Bimber, B. N., Moreland, A. J., Wiseman, R. W., Hughes, A. L., O'Connor, D. H. (2008). Complete Characterization of Killer Ig-Like Receptor (KIR) Haplotypes in Mauritian Cynomolgus Macaques: Novel Insights into Nonhuman Primate KIR Gene Content and Organization. J. Immunol. 181: 6301-6308 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»