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Author Notes:

Aron E. Lukacher, Dept. of Pathology, Woodruff Memorial Research Building, 1639 Pierce Dr., Atlanta, GA 30322., Phone: 404-727-1896, Fax: 404-727-5764. Aron E. Lukacher: ude.yrome@hcakula

We thank Robert Karaffa for technical assistance for FACS® sorting and Laurie Harrington for helpful discussions.

Subjects:

Research Funding:

This work was supported by National Institutes of Health grants CA71971 (to A.E. Lukacher) and AI42373 (to J.D. Altman).

Keywords:

  • CD8+ T lymphocytes
  • intracellular IFN-γ
  • neonatal mice
  • polyoma virus
  • tetramers

Antiviral Cd8+ T Cell Responses in Neonatal Mice

Tools:

Journal Title:

Journal of Experimental Medicine

Volume:

Volume 193, Number 5

Publisher:

, Pages 595-606

Type of Work:

Article | Final Publisher PDF

Abstract:

Polyoma virus is a potent oncogenic pathogen when inoculated into newborn mice of particular H-2k strains. Using Dk tetramers containing the dominant antipolyoma CD8+ T cell epitope, middle T protein (MT)389–397, and intracellular interferon γ staining, we enumerated MT389-specific CD8+ T cells in infected neonates having opposite susceptibilities to polyoma virus–induced tumors. In resistant mice, MT389-specific CD8+ T cells dramatically expanded during acute infection in neonates to a frequency rivaling that in adults; furthermore, in both neonatal and adult mice, this antipolyoma CD8+ T cell response exhibited nearly identical T cell receptor (TCR) functional avidities and TCR functional fingerprints. Susceptible mice mounted an MT389-specific CD8+ T cell response of only fourfold lower magnitude than resistant mice; but, in clear contrast to resistant mice, these CD8+ T cells lacked ex vivo MT389-specific cytotoxic activity. However, MT389-specific CD8+ T cells in resistant and susceptible mice expressed similar TCR avidities, perforin levels, and surface type O-glycan levels indicative of mature CD8+ T cell effectors. Upon in vitro restimulation with infected antigen-presenting cells, CD8+ T cells from acutely infected susceptible neonates acquired strong MT389-specific cytotoxicity. These findings indicate that polyoma-specific CD8+ T cells are armed with, but restrained from deploying, their cytotoxic effector function in mice susceptible to polyoma virus tumorigenesis.

Copyright information:

© 2001 The Rockefeller University Press

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-nc-sa/4.0/).

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