Antiviral CD8+ T cell responses in neonatal mice: Susceptibility to polyoma virus-induced tumors is associated with lack of cytotoxic function by viral antigen-specific T cells

Janice M. Moser, John D. Altman, Aron E. Lukacher

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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.

Original languageEnglish (US)
Pages (from-to)595-605
Number of pages11
JournalJournal of Experimental Medicine
Volume193
Issue number5
DOIs
StatePublished - Mar 5 2001

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Polyomavirus
Viral Antigens
Antiviral Agents
T-Lymphocytes
Neoplasms
T-Cell Antigen Receptor
Perforin
T-Lymphocyte Epitopes
Dermatoglyphics
Antigen-Presenting Cells
Interferons
Polysaccharides
Carcinogenesis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

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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.",
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