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


Journal Article

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.

Full Text

Cited Authors

  • Yang, Y; Huang, C-T; Huang, X; Pardoll, DM

Published Date

  • May 2004

Published In

Volume / Issue

  • 5 / 5

Start / End Page

  • 508 - 515

PubMed ID

  • 15064759

Pubmed Central ID

  • 15064759

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1059


  • eng