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 Xiong, Y.
Right arrow Articles by MacDonald, K. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xiong, Y.
Right arrow Articles by MacDonald, K. S.

 Previous Article  |  Next Article 

Journal of Virology, March 2001, p. 3028-3033, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.3028-3033.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Simian Immunodeficiency Virus (SIV) Infection of a Rhesus Macaque Induces SIV-Specific CD8+ T Cells with a Defect in Effector Function That Is Reversible on Extended Interleukin-2 Incubation

Yelin Xiong,1 Mark A. Luscher,1,2 John D. Altman,3 Michael Hulsey,3 Harriet L. Robinson,3 Mario Ostrowski,1 Brian H. Barber,4 and Kelly S. MacDonald1,4,5,*

Department of Medicine1 and Department of Immunology,4 University of Toronto, Department of Microbiology, Mount Sinai Hospital,5 and University Health Network,2 Toronto, Ontario, Canada, and Emory University Vaccine Center, Atlanta, Georgia3

Received 15 September 2000/Accepted 14 December 2000

A vigorous expansion of antigen-specific CD8+ T cells lacking apparent effector function was observed in a rhesus macaque acutely infected with the simian immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8+ T cells were identified using antigenic-peptide class I major histocompatibility complex tetramers. As many as 8.3% of CD8+ cells recognized the Mamu-A*01-associated SIV epitope Gag181-189 (CTPYDINQM); however, these cells demonstrated no effector function when presented with peptide-incubated targets, as measured by intracellular cytokine staining for gamma interferon (IFN-gamma ), interleukin-2 (IL-2) production, or direct cellular lysis. Similar results were observed with three other SIV peptide antigens. Nonresponsiveness did not correlate with apoptosis of the CD8+ cells, nor were cells from this macaque impaired in their ability to present peptide antigens. Associated with the nonresponsive state was a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2 treatment for 1 week in the absence of antigenic stimulation restored antigen-specific responses and the quantitative correlation between tetramer recognition and antigen-responsive IFN-gamma secretion. This case report suggests a regulatory mechanism that may impede the effector function of antigen-specific T cells during acute infection with SIV or human immunodeficiency virus in some cases. This mechanism may participate in the failure of the immune system to limit infection.

* Corresponding author. Mailing address: Department of Microbiology, Mount Sinai Hospital, 600 University Ave., Toronto, ON M5G 1X5, Canada Phone: (416) 586-8879. Fax: (416) 586-8746. E-mail: KMacDonald{at}MtSinai.on.ca

Journal of Virology, March 2001, p. 3028-3033, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.3028-3033.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Blattman, J. N., Wherry, E. J., Ha, S.-J., van der Most, R. G., Ahmed, R. (2009). Impact of Epitope Escape on PD-1 Expression and CD8 T-Cell Exhaustion during Chronic Infection. J. Virol. 83: 4386-4394 [Abstract] [Full Text]  
  • Plesa, G., Snook, A. E., Waldman, S. A., Eisenlohr, L. C. (2008). Derivation and Fluidity of Acutely Induced Dysfunctional CD8+ T Cells. J. Immunol. 180: 5300-5308 [Abstract] [Full Text]  
  • Petrovas, C., Price, D. A., Mattapallil, J., Ambrozak, D. R., Geldmacher, C., Cecchinato, V., Vaccari, M., Tryniszewska, E., Gostick, E., Roederer, M., Douek, D. C., Morgan, S. H., Davis, S. J., Franchini, G., Koup, R. A. (2007). SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood 110: 928-936 [Abstract] [Full Text]  
  • Miller, N. E., Bonczyk, J. R., Nakayama, Y., Suresh, M. (2005). Role of Thymic Output in Regulating CD8 T-Cell Homeostasis during Acute and Chronic Viral Infection. J. Virol. 79: 9419-9429 [Abstract] [Full Text]  
  • Monceaux, V., Viollet, L., Petit, F., Fang, R. H. T., Cumont, M.-C., Zaunders, J., Hurtrel, B., Estaquier, J. (2005). CD8+ T Cell Dynamics during Primary Simian Immunodeficiency Virus Infection in Macaques: Relationship of Effector Cell Differentiation with the Extent of Viral Replication. J. Immunol. 174: 6898-6908 [Abstract] [Full Text]  
  • Koneru, M., Schaer, D., Monu, N., Ayala, A., Frey, A. B. (2005). Defective Proximal TCR Signaling Inhibits CD8+ Tumor-Infiltrating Lymphocyte Lytic Function. J. Immunol. 174: 1830-1840 [Abstract] [Full Text]  
  • Wherry, E. J., Ahmed, R. (2004). Memory CD8 T-Cell Differentiation during Viral Infection. J. Virol. 78: 5535-5545 [Full Text]  
  • Zhou, S., Ou, R., Huang, L., Price, G. E., Moskophidis, D. (2004). Differential Tissue-Specific Regulation of Antiviral CD8+ T-Cell Immune Responses during Chronic Viral Infection. J. Virol. 78: 3578-3600 [Abstract] [Full Text]  
  • Chang, J., Choi, S. Y., Jin, H. T., Sung, Y. C., Braciale, T. J. (2004). Improved Effector Activity and Memory CD8 T Cell Development by IL-2 Expression during Experimental Respiratory Syncytial Virus Infection. J. Immunol. 172: 503-508 [Abstract] [Full Text]  
  • Mitchell, K. A., Lawrence, B. P. (2003). Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) Renders Influenza Virus-Specific CD8+ T Cells Hyporesponsive to Antigen. Toxicol Sci 74: 74-84 [Abstract] [Full Text]  
  • Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R., Ahmed, R. (2003). Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment. J. Virol. 77: 4911-4927 [Abstract] [Full Text]  
  • Leavey, J. K., Tarleton, R. L. (2003). Cutting Edge: Dysfunctional CD8+ T Cells Reside in Nonlymphoid Tissues During Chronic Trypanosoma cruzi Infection. J. Immunol. 170: 2264-2268 [Abstract] [Full Text]  
  • Horton, H., Vogel, T. U., Carter, D. K., Vielhuber, K., Fuller, D. H., Shipley, T., Fuller, J. T., Kunstman, K. J., Sutter, G., Montefiori, D. C., Erfle, V., Desrosiers, R. C., Wilson, N., Picker, L. J., Wolinsky, S. M., Wang, C., Allison, D. B., Watkins, D. I. (2002). Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239. J. Virol. 76: 7187-7202 [Abstract] [Full Text]  
  • Catalina, M. D., Sullivan, J. L., Brody, R. M., Luzuriaga, K. (2002). Phenotypic and Functional Heterogeneity of EBV Epitope-Specific CD8+ T Cells. J. Immunol. 168: 4184-4191 [Abstract] [Full Text]  
  • Greten, T. F., Schneck, J. P. (2002). Development and Use of Multimeric Major Histocompatibility Complex Molecules. CVI 9: 216-220 [Full Text]  
  • McKay, P. F., Schmitz, J. E., Barouch, D. H., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Gorgone, D. A., Letvin, N. L. (2002). Vaccine Protection Against Functional CTL Abnormalities in Simian Human Immunodeficiency Virus-Infected Rhesus Monkeys. J. Immunol. 168: 332-337 [Abstract] [Full Text]  
  • Eo, S. K., Kumaraguru, U., Rouse, B. T. (2001). Plasmid DNA Encoding CCR7 Ligands Compensate for Dysfunctional CD8+ T Cell Responses by Effects on Dendritic Cells. J. Immunol. 167: 3592-3599 [Abstract] [Full Text]  
  • Welsh, R. M. (2001). Assessing Cd8 T Cell Number and Dysfunction in the Presence of Antigen. JEM 193: f19-f22 [Full Text]  
  • Reignat, S., Webster, G. J.M., Brown, D., Ogg, G. S., King, A., Seneviratne, S. L., Dusheiko, G., Williams, R., Maini, M. K., Bertoletti, A. (2002). Escaping High Viral Load Exhaustion: CD8 Cells with Altered Tetramer Binding in Chronic Hepatitis B Virus Infection. JEM 195: 1089-1101 [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»