期刊
JOURNAL OF IMMUNOTHERAPY
卷 28, 期 3, 页码 220-228出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.cji.0000156828.75196.0d
关键词
OT-1; CD8(+) T cells; dsRNA; poly(I : C); IFN-gamma; NK cells; B16-OVA; EG.7
资金
- NCI NIH HHS [1 R01 CA94856-01] Funding Source: Medline
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-gamma and TNF-alpha 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据