Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection

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

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49 Scopus citations

Abstract

T cells are critical for clearing infection and preventing tumors induced by polyoma virus, a natural murine papovavirus. We previously identified the immunodominant epitope for polyoma virus-specific CTL in tumor-resistant H-2(k) mice as the D(k)restricted peptide, MT389-397, derived from the polyoma middle T oncoprotein. In this study, we developed tetrameric D(k) complexes containing the MT389-397 peptide to directly visualize and enumerate MT389-397-specific CTL during polyoma virus infection. We found that D(k)/MT389 tetramer+CD8+ T cells undergo a massive expansion during primary infection such that by day 7 postinfection these Ag-specific CD8+ T cells constitute ~20% of the total and ~40% of the activated CD8+ T cells in the spleen. This expansion of D(k)/MT389 tetramer+CD8+ T cells parallels the emergence of MT389-397-specific ex vivo cytolytic activity and clearance of polyoma virus. Notably, D(k)/MT389 tetramer+CD8+ T cells are maintained in memory at very high levels. The frequencies of D(k)/MT389 tetramer+CD8+ effector and memory T cells in vivo match those of CD8+ T cells producing intracellular IFN-γ after 6-h in vitro stimulation by MT389-397 peptide. Consistent with preferential Vβ6 expression by MT389-397-specific CD8+CTL lines and clones, D(k)/MT389 tetramer+CD8+ T cells exhibit biased expression of this Vβ gene segment. Finally, we show that D(k)/MT389 tetramer+CD8+ T cells efficiently infiltrate a polyoma tumor challenge to virus-immune mice. Taken together, these findings strongly implicate virus- induced MT389-397-specific CD8+ T cells as essential effectors in eliminating polyoma-infected and polyoma-transformed cells in vivo.

Original languageEnglish (US)
Pages (from-to)3369-3378
Number of pages10
JournalJournal of Immunology
Volume163
Issue number6
StatePublished - Sep 15 1999

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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