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 Zelinskyy, G.
Right arrow Articles by Dittmer, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zelinskyy, G.
Right arrow Articles by Dittmer, U.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10619-10626, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10619-10626.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD8+ T-Cell Dysfunction due to Cytolytic Granule Deficiency in Persistent Friend Retrovirus Infection

Gennadiy Zelinskyy,1 Shelly J. Robertson,2 Simone Schimmer,1 Ronald J. Messer,2 Kim J. Hasenkrug,2,{dagger} and Ulf Dittmer1,{dagger}*

Institut fuer Virologie des Universitaetsklinikums Essen, Essen, Germany,1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana2

Received 18 January 2005/ Accepted 20 May 2005

Virus-specific CD8+ T cells are critical for the control of acute Friend virus (FV) infections, but are rendered impotent by CD4+ regulatory T cells during the chronic phase of infection. The current study examines this CD8+ T-cell dysfunction by analyzing the production and release of cytolytic molecules by CD8+ T cells. CD8+ T cells with an activated phenotype (CD43+) from acutely infected mice produced all three key components of lytic granules: perforin, granzyme A, and granzyme B. Furthermore, they displayed evidence of recent degranulation and in vivo cytotoxicity. In contrast, activated CD8+ T cells from chronically infected mice were deficient in cytolytic molecules and showed little evidence of recent degranulation and poor in vivo cytotoxicity. Evidence from tetramer-positive CD8+ T cells with known virus specificity confirmed the findings from the activated subset of CD8+ T cells. Interestingly, perforin and granzyme A mRNA levels were not significantly reduced during chronic infection, indicating control at a posttranscriptional level. Granzyme B deficiency was associated with a significant decrease in mRNA levels, but posttranscriptional control also appeared to contribute to deficiency. These results demonstrate a broad impairment of cytotoxic CD8+ T-cell effector function during chronic retroviral infection and explain the inability of virus-specific CD8+ T cells to eliminate persistent virus.

* Corresponding author. Mailing address: Institut fuer Virologie, Universitaetsklinikum Essen, 45122 Essen, Germany. Phone: 49(201) 7233693. Fax: +49(201) 723-5929. E-mail:ulf.dittmer{at}uni-essen.de.

{dagger} Both authors contributed equally to the design and documentation of this study.

Journal of Virology, August 2005, p. 10619-10626, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10619-10626.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zelinskyy, G., Dietze, K. K., Husecken, Y. P., Schimmer, S., Nair, S., Werner, T., Gibbert, K., Kershaw, O., Gruber, A. D., Sparwasser, T., Dittmer, U. (2009). The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 114: 3199-3207 [Abstract] [Full Text]  
  • Myers, L., Messer, R. J., Carmody, A. B., Hasenkrug, K. J. (2009). Tissue-Specific Abundance of Regulatory T Cells Correlates with CD8+ T Cell Dysfunction and Chronic Retrovirus Loads. J. Immunol. 183: 1636-1643 [Abstract] [Full Text]  
  • Robertson, S. J., Messer, R. J., Carmody, A. B., Mittler, R. S., Burlak, C., Hasenkrug, K. J. (2008). CD137 Costimulation of CD8+ T Cells Confers Resistance to Suppression by Virus-Induced Regulatory T Cells. J. Immunol. 180: 5267-5274 [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»