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

Polyoma virus is a potent oncogenic pathogen when inoculated into newborn mice of particular H-2^k strains. Using D^k 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.