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 m ice of particular H-2(k) strains. Using D-k tetramers containing the domina nt antipolyoma CD8(+) T cell epitope, middle T protein (MT)389-397, and int racellular interferon gamma staining, we enumerated MT389-specific CD8(+) T cells in infected neonates having opposite susceptibilities to polyoma vir us-induced tumors. In resistant mice, MT389-specific CD8(+) T cells dramati cally expanded during acute infection in neonates to a frequency rivaling t hat in adults; furthermore, in both neonatal and adult mice, this antipolyo ma CD8(+) T cell response exhibited nearly identical T cell receptor (TCR) functional avidities and TCR functional fingerprints. Susceptible mice moun ted an MT389-specific CD8(+) T cell response of only fourfold lower magnitu de than resistant mice; but, in clear contrast to resistant mice, these CD8 (+) T cells lacked ex vivo MT389-specific cytotoxic activity. However, MT38 9-specific CD8(+) T cells in resistant and susceptible mice expressed simil ar TCR avidities, perforin levels, and surface type O-glycan levels indicat ive of mature CD8(+) T cell effectors. Upon in vitro restimulation with inf ected antigen-presenting cells, CD8(+) T cells from acutely infected suscep tible neonates acquired strong MT389-specific cytotoxicity. These findings indicate that polyoma-specific CD8(+) T cells are armed with, but restraine d from deploying, their cytotoxic effector function in mice susceptible to polyoma virus tumorigenesis.