Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling: Evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity

Mohamed L. Salem, Andre N. Kadima, David J. Cole, William E. Gillanders

Research output: Contribution to journalArticlepeer-review

126 Scopus citations

Abstract

Poly(I:C), a synthetic double-stranded RNA polymer and a TLR3 agonist, can be used as a vaccine adjuvant to enhance adaptive immunity. However, the antigen-specific CD8 T-cell response to peptide vaccination and poly(I:C) has not been clearly defined. Here, the authors characterized the antigen-specific CD8 T-cell response to peptide vaccination and poly(I:C) and specifically addressed the hypothesis that poly(I:C) can enhance antitumor immunity. To define the antigen-specific T-cell response, the authors established a model based on the adoptive transfer of T cells from the OT-1 T-cell receptor transgenic mouse. In this model, vaccination with peptide alone resulted in a limited, transient expansion of antigen-specific CD8 T cells. In contrast, peptide vaccination with concomitant administration of poly(I:C) resulted in a dramatic sustained increase in the number of antigen-specific CD8 T cells. This increase in cell number was associated with an increase in CD8 T-cell function, as defined by specific IFN-γ and TNF-α production, and protection from tumor challenge. The adjuvant effects of poly(I:C) appear to be at least partially dependent on an increase in the transcription of the anti-apoptotic molecules Bcl-3 and Bcl-xL and a concomitant decrease in apoptosis during the contraction phase of the primary T-cell response. In addition, administration of poly(I:C) enhanced the response to a nonimmunogenic self-antigen in a dendritic cell vaccine-based vaccine strategy. Collectively, these results confirm the potential of poly(I:C) as a vaccine adjuvant and suggest that targeting of TLR3 is likely to be a valuable addition to peptide-based vaccination strategies.

Original languageEnglish
Pages (from-to)220-228
Number of pages9
JournalJournal of Immunotherapy
Volume28
Issue number3
DOIs
StatePublished - 2005

Keywords

  • B16-OVA
  • EG.7
  • IFN-γ
  • NK cells
  • OT-1 CD8 T cells
  • Poly(I:C)
  • dsRNA

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