Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance

Yiping Yang, Chang Tai Huang, Xiaopei Huang, Drew M. Pardoll

Research output: Contribution to journalArticle

Abstract

One chief barrier to cancer immunotherapy is tumor-specific T cell tolerance. Here we compared the ability of hemagglutinin (HA)-encoding recombinant viruses versus 'HA-loaded' dendritic cells to reverse HA-specific CD8 tolerance and to protect mice from tumor challenge. Both vaccines were comparable in activating naive HA-specific CD8+ T cells. However, in circumstances of established tolerance, viral vaccines could break CD8 tolerance in the presence of CD4+CD25+ regulatory T cells, whereas dendritic cell-based vaccines achieved this only after removal of regulatory T cells or the coadministration of a Toll-like receptor (TLR) ligand or irrelevant virus. These results demonstrate that virus provides TLR signals required for bypassing regulatory T cell-mediated tolerance and emphasize the importance of persistent TLR signals for immunotherapy in the setting of established tolerance.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalNature Immunology
Volume5
Issue number5
DOIs
StatePublished - May 1 2004

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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