The Journal of Experimental Medicine
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Published online 5 March 2001.
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© The Rockefeller University Press, 0022-1007/2001/3/595/ $5.00
The Journal of Experimental Medicine, Volume 193, Number 5, March 5, 2001 595-606

Original Article

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. Mosera, John D. Altmanb,c, and Aron E. Lukachera
a Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322
b Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322
c Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322

Correspondence to: Aron E. Lukacher, Dept. of Pathology, Woodruff Memorial Research Building, 1639 Pierce Dr., Atlanta, GA 30322. Tel:404-727-1896 Fax:404-727-5764 E-mail:alukach{at}emory.edu.

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 {gamma} 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.

Key Words: CD8+ T lymphocytes, intracellular IFN-{gamma}, neonatal mice, polyoma virus, tetramers


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