TY - JOUR
T1 - Defining the antigen-specific T-cell response to vaccination and poly(I:C)/TLR3 signaling
T2 - Evidence of enhanced primary and memory CD8 T-cell responses and antitumor immunity
AU - Salem, Mohamed L.
AU - Kadima, Andre N.
AU - Cole, David J.
AU - Gillanders, William E.
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - B16-OVA
KW - EG.7
KW - IFN-γ
KW - NK cells
KW - OT-1 CD8 T cells
KW - Poly(I:C)
KW - dsRNA
UR - http://www.scopus.com/inward/record.url?scp=17844384773&partnerID=8YFLogxK
U2 - 10.1097/01.cji.0000156828.75196.0d
DO - 10.1097/01.cji.0000156828.75196.0d
M3 - Article
C2 - 15838378
AN - SCOPUS:17844384773
SN - 1524-9557
VL - 28
SP - 220
EP - 228
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
IS - 3
ER -