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Journal of Virology, April 2003, p. 4911-4927, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4911-4927.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment

E. John Wherry, Joseph N. Blattman,{dagger} Kaja Murali-Krishna,{ddagger} Robbert van der Most,§ and Rafi Ahmed*

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 12 September 2002/ Accepted 4 December 2002

Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. However, how persisting virus impacts various CD8 T-cell effector functions and influences other aspects of CD8 T-cell dynamics, such as immunodominance and tissue distribution, remains largely unknown. Using different strains of lymphocytic choriomeningitis virus (LCMV), we compared responses to the same CD8 T-cell epitopes during acute or chronic infection. Persistent infection led to a disruption of the normal immunodominance hierarchy of CD8 T-cell responses seen following acute infection and dramatically altered the tissue distribution of LCMV-specific CD8 T cells in lymphoid and nonlymphoid tissues. Most importantly, CD8 T-cell functional impairment occurred in a hierarchical fashion in chronically infected mice. Production of interleukin 2 and the ability to lyse target cells in vitro were the first functions compromised, followed by the ability to make tumor necrosis factor alpha, while gamma interferon production was most resistant to functional exhaustion. Antigen appeared to be the driving force for this loss of function, since a strong correlation existed between the viral load and the level of exhaustion. Further, epitopes presented at higher levels in vivo resulted in physical deletion, while those presented at lower levels induced functional exhaustion. A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells. These results have implications for the study of human chronic infections, where similar T-cell deletion and functional dysregulation has been observed.

* Corresponding author. Mailing address: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Building, 1510 Clifton Rd., Atlanta, GA 30322. Phone: (404) 727-4700. Fax: (404) 727-3722. E-mail: ra{at}microbio.emory.edu.

{dagger} Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024.

{ddagger} Present address: Department of Immunology, H574 HSC, University of Washington, Seattle, WA 98195.

§ Present address: Department of Immunology, Faculty of Veterinary Medicine, 3584 CL Utrecht, The Netherlands.

Journal of Virology, April 2003, p. 4911-4927, Vol. 77, No. 8
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.8.4911-4927.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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  • Belnoue, E., Fontannaz-Bozzotti, P., Grillet, S., Lambert, P.-H., Siegrist, C.-A. (2007). Protracted Course of Lymphocytic Choriomeningitis Virus WE Infection in Early Life: Induction but Limited Expansion of CD8+ Effector T Cells and Absence of Memory CD8+ T Cells. J. Virol. 81: 7338-7350 [Abstract] [Full Text]  
  • Mothe, B. R., Stewart, B. S., Oseroff, C., Bui, H.-H., Stogiera, S., Garcia, Z., Dow, C., Rodriguez-Carreno, M. P., Kotturi, M., Pasquetto, V., Botten, J., Crotty, S., Janssen, E., Buchmeier, M. J., Sette, A. (2007). Chronic Lymphocytic Choriomeningitis Virus Infection Actively Down-Regulates CD4+ T Cell Responses Directed against a Broad Range of Epitopes. J. Immunol. 179: 1058-1067 [Abstract] [Full Text]  
  • Whitmire, J. K., Eam, B., Benning, N., Whitton, J. L. (2007). Direct Interferon-{gamma} Signaling Dramatically Enhances CD4+ and CD8+ T Cell Memory. J. Immunol. 179: 1190-1197 [Abstract] [Full Text]  
  • Cush, S. S., Anderson, K. M., Ravneberg, D. H., Weslow-Schmidt, J. L., Flano, E. (2007). Memory Generation and Maintenance of CD8+ T Cell Function during Viral Persistence. J. Immunol. 179: 141-153 [Abstract] [Full Text]  
  • Russell, M. S., Iskandar, M., Mykytczuk, O. L., Nash, J. H. E., Krishnan, L., Sad, S. (2007). A Reduced Antigen Load In Vivo, Rather Than Weak Inflammation, Causes a Substantial Delay in CD8+ T Cell Priming against Mycobacterium bovis (Bacillus Calmette-Guerin). J. Immunol. 179: 211-220 [Abstract] [Full Text]  
  • Plunkett, F. J., Franzese, O., Finney, H. M., Fletcher, J. M., Belaramani, L. L., Salmon, M., Dokal, I., Webster, D., Lawson, A. D. G., Akbar, A. N. (2007). The Loss of Telomerase Activity in Highly Differentiated CD8+CD28-CD27- T Cells Is Associated with Decreased Akt (Ser473) Phosphorylation. J. Immunol. 178: 7710-7719 [Abstract] [Full Text]  
  • Andrews, N. P., Pack, C. D., Vezys, V., Barber, G. N., Lukacher, A. E. (2007). Early Virus-Associated Bystander Events Affect the Fitness of the CD8 T Cell Response to Persistent Virus Infection. J. Immunol. 178: 7267-7275 [Abstract] [Full Text]  
  • Shin, H., Blackburn, S. D., Blattman, J. N., Wherry, E. J. (2007). Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. JEM 204: 941-949 [Abstract] [Full Text]  
  • Gehring, A. J., Sun, D., Kennedy, P. T. F., Nolte-'t Hoen, E., Lim, S. G., Wasser, S., Selden, C., Maini, M. K., Davis, D. M., Nassal, M., Bertoletti, A. (2007). The Level of Viral Antigen Presented by Hepatocytes Influences CD8 T-Cell Function. J. Virol. 81: 2940-2949 [Abstract] [Full Text]  
  • Hasegawa, A., Moriya, C., Liu, H., Charini, W. A., Vinet, H. C., Subbramanian, R. A., Sen, P., Letvin, N. L., Kuroda, M. J. (2007). Analysis of TCR{alpha}beta Combinations used by Simian Immunodeficiency Virus-Specific CD8+ T Cells in Rhesus Monkeys: Implications for CTL Immunodominance. J. Immunol. 178: 3409-3417 [Abstract] [Full Text]  
  • Agnellini, P., Wolint, P., Rehr, M., Cahenzli, J., Karrer, U., Oxenius, A. (2007). Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection. Proc. Natl. Acad. Sci. USA 104: 4565-4570 [Abstract] [Full Text]  
  • Geldmacher, C., Currier, J. R., Herrmann, E., Haule, A., Kuta, E., McCutchan, F., Njovu, L., Geis, S., Hoffmann, O., Maboko, L., Williamson, C., Birx, D., Meyerhans, A., Cox, J., Hoelscher, M. (2007). CD8 T-Cell Recognition of Multiple Epitopes within Specific Gag Regions Is Associated with Maintenance of a Low Steady-State Viremia in Human Immunodeficiency Virus Type 1-Seropositive Patients. J. Virol. 81: 2440-2448 [Abstract] [Full Text]  
  • Lee, S., Miller, S. A., Wright, D. W., Rock, M. T., Crowe, J. E. Jr. (2007). Tissue-Specific Regulation of CD8+ T-Lymphocyte Immunodominance in Respiratory Syncytial Virus Infection. J. Virol. 81: 2349-2358 [Abstract] [Full Text]  
  • Ford, M. L., Koehn, B. H., Wagener, M. E., Jiang, W., Gangappa, S., Pearson, T. C., Larsen, C. P. (2007). Antigen-specific precursor frequency impacts T cell proliferation, differentiation, and requirement for costimulation. JEM 204: 299-309 [Abstract] [Full Text]  
  • Bengsch, B., Spangenberg, H. C., Kersting, N., Neumann-Haefelin, C., Panther, E., von Weizsacker, F., Blum, H. E., Pircher, H., Thimme, R. (2007). Analysis of CD127 and KLRG1 Expression on Hepatitis C Virus-Specific CD8+ T Cells Reveals the Existence of Different Memory T-Cell Subsets in the Peripheral Blood and Liver. J. Virol. 81: 945-953 [Abstract] [Full Text]  
  • Sheridan, B. S., Khanna, K. M., Frank, G. M., Hendricks, R. L. (2006). Latent Virus Influences the Generation and Maintenance of CD8+ T Cell Memory. J. Immunol. 177: 8356-8364 [Abstract] [Full Text]  
  • Crotty, S., McCausland, M. M., Aubert, R. D., Wherry, E. J., Ahmed, R. (2006). Hypogammaglobulinemia and exacerbated CD8 T-cell-mediated immunopathology in SAP-deficient mice with chronic LCMV infection mimics human XLP disease. Blood 108: 3085-3093 [Abstract] [Full Text]  
  • van Leeuwen, E. M. M., Remmerswaal, E. B. M., Heemskerk, M. H. M., ten Berge, I. J. M., van Lier, R. A. W. (2006). Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection. Blood 108: 3121-3127 [Abstract] [Full Text]  
  • Vezys, V., Masopust, D., Kemball, C. C., Barber, D. L., O'Mara, L. A., Larsen, C. P., Pearson, T. C., Ahmed, R., Lukacher, A. E. (2006). Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. JEM 203: 2263-2269 [Abstract] [Full Text]  
  • Obar, J. J., Fuse, S., Leung, E. K., Bellfy, S. C., Usherwood, E. J. (2006). Gammaherpesvirus persistence alters key CD8 T-cell memory characteristics and enhances antiviral protection.. J. Virol. 80: 8303-8315 [Abstract] [Full Text]  
  • Grayson, J. M., Weant, A. E., Holbrook, B. C., Hildeman, D. (2006). Role of Bim in Regulating CD8+ T-Cell Responses during Chronic Viral Infection.. J. Virol. 80: 8627-8638 [Abstract] [Full Text]  
  • Yi, J. S., Holbrook, B. C., Michalek, R. D., Laniewski, N. G., Grayson, J. M. (2006). Electron Transport Complex I Is Required for CD8+ T Cell Function. J. Immunol. 177: 852-862 [Abstract] [Full Text]  
  • Jabbari, A., Harty, J. T. (2006). The generation and modulation of antigen-specific memory CD8 T cell responses. J. Leukoc. Biol. 80: 16-23 [Abstract] [Full Text]  
  • York, I. A., Brehm, M. A., Zendzian, S., Towne, C. F., Rock, K. L. (2006). Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance. Proc. Natl. Acad. Sci. USA 103: 9202-9207 [Abstract] [Full Text]  
  • Kedzierska, K., Venturi, V., Field, K., Davenport, M. P., Turner, S. J., Doherty, P. C. (2006). Early establishment of diverse T cell receptor profiles for influenza-specific CD8+CD62Lhi memory T cells. Proc. Natl. Acad. Sci. USA 103: 9184-9189 [Abstract] [Full Text]  


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