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Journal of Virology, May 2008, p. 4697-4705, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02698-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Generation of Antiviral Major Histocompatibility Complex Class I-Restricted T Cells in the Absence of CD8 Coreceptors {triangledown}

Nicolas P. Andrews, Christopher D. Pack, and Aron E. Lukacher*

Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 19 December 2007/ Accepted 29 February 2008

The CD8 coreceptor is important for positive selection of major histocompatibility complex I (MHC-I)-restricted thymocytes and in the generation of pathogen-specific T cells. However, the requirement for CD8 in these processes may not be essential. We previously showed that mice lacking β2-microglobulin are highly susceptible to tumors induced by mouse polyoma virus (PyV), but CD8-deficient mice are resistant to these tumors. In this study, we show that CD8-deficient mice also control persistent PyV infection as efficiently as wild-type mice and generate a substantial virus-specific, MHC-I-restricted, T-cell response. Infection with vesicular stomatitis virus (VSV), which is acutely cleared, also recruited antigen-specific, MHC-I-restricted T cells in CD8-deficient mice. Yet, unlike in VSV infection, the antiviral MHC-I-restricted T-cell response to PyV has a prolonged expansion phase, indicating a requirement for persistent infection in driving T-cell inflation in CD8-deficient mice. Finally, we show that the PyV-specific, MHC-I-restricted T cells in CD8-deficient mice, while maintained long term at near-wild-type levels, are short lived in vivo and have extremely narrow T-cell receptor repertoires. These findings provide a possible explanation for the resistance of CD8-deficient mice to PyV-induced tumors and have implications for the maintenance of virus-specific MHC-I-restricted T cells during persistent infection.

* Corresponding author. Mailing address: Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Room 7307, 101 Woodruff Circle, Atlanta, GA 30322. Phone: (404) 727-1896. Fax: (404) 727-5764. E-mail: alukach{at}emory.edu

{triangledown} Published ahead of print on 12 March 2008.

Journal of Virology, May 2008, p. 4697-4705, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02698-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Swanson, P. A. II, Hofstetter, A. R., Wilson, J. J., Lukacher, A. E. (2009). Cutting Edge: Shift in Antigen Dependence by an Antiviral MHC Class Ib-Restricted CD8 T Cell Response during Persistent Viral Infection. J. Immunol. 182: 5198-5202 [Abstract] [Full Text]  
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  • Angelov, G. S., Guillaume, P., Luescher, I. F. (2009). CD8{beta} knockout mice mount normal anti-viral CD8+ T cell responses--but why?. Int Immunol 21: 123-135 [Abstract] [Full Text]  
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