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Journal of Virology, October 2002, p. 9657-9663, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9657-9663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Susceptibility to Polyomavirus-Induced Tumors in Inbred Mice: Role of Innate Immune Responses

Palanivel Velupillai, John P. Carroll, and Thomas L. Benjamin*

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115

Received 1 May 2002/ Accepted 19 June 2002

Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by polyomavirus and transmit their susceptibility in a dominant manner in crosses with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus infection with a type 1 cytokine response and develop effective cell-mediated immunity to the virus-induced tumors. By enumerating virus-specific CD8+ T cells and measuring cytokine responses, we show that the susceptibility of PE mice is due to the absence of a type 1 cytokine response and a concomitant failure to sustain virus-specific cytotoxic T lymphocytes. (PE x BR)F1 mice showed an initial type 1 response that became skewed toward type 2. Culture supernatants of splenocytes from infected PE mice stimulated in vitro contained high levels of interleukin-10 and no detectable gamma interferon, while those from BR mice showed the opposite pattern. Differences in the innate immune response to polyomavirus by antigen-presenting cells in PE mice and BR mice led to polarization of T-cell cytokine responses. Adherent cells from spleens of infected BR mice produced high levels of interleukin-12, while those from infected PE and F1 mice produced predominantly interleukin-10. PE and F1 mice infected by polyomavirus responded with increases in antigen-presenting cells expressing B7.2 costimulatory molecules, whereas BR mice responded with increased expression of B7.1. Administration of recombinant interleukin-12 along with virus resulted in partial protection of PE mice and provided complete protection against tumor development in F1 animals.

* Corresponding author. Mailing address: Department of Pathology, Armenise-230, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 432-1960. Fax: (617) 277-5291. E-mail: thomas_benjamin{at}hms.harvard.edu.

Journal of Virology, October 2002, p. 9657-9663, Vol. 76, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.19.9657-9663.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Yadav, D., Sarvetnick, N. (2007). B7-2 Regulates Survival, Phenotype, and Function of APCs. J. Immunol. 178: 6236-6241 [Abstract] [Full Text]  
  • Velupillai, P., Garcea, R. L., Benjamin, T. L. (2006). Polyoma Virus-Like Particles Elicit Polarized Cytokine Responses in APCs from Tumor-Susceptible and -Resistant Mice. J. Immunol. 176: 1148-1153 [Abstract] [Full Text]  
  • Welton, A. R., Chesler, E. J., Sturkie, C., Jackson, A. U., Hirsch, G. N., Spindler, K. R. (2005). Identification of Quantitative Trait Loci for Susceptibility to Mouse Adenovirus Type 1. J. Virol. 79: 11517-11522 [Abstract] [Full Text]  


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