Vet Med - Czech, 2011, 56(12):602-611 | DOI: 10.17221/4438-VETMED

TLR agonists activate HPV11 E7-pulsed DCs to promote a specific T cell response in a murine model

X.H. Mao¹, X.Z. Chen², W.W. Zhang¹, J.Y. Wang¹, L.F. Liu¹, Q. Zhou², K.J. Zhu², H. Cheng²

¹ Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

² Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

: Some TLR agonists may up-regulate the activation of dendritic cells caused by viral antigenic peptides and antigen-specific cytotoxic T lymphocytes, which are crucial in HPV vaccine development. We investigated the ability of three TLR agonists, imiquimod, PIC and CpG, to stimulate the maturation of murine BM-DCs loaded with HPV11E7 CTL epitopes, and the subsequent effect on HPV-specific T cell responses and tumour protection in a C57BL/6 mouse model. We found that TLR agonists, mostly PIC and imiquimod, stimulated the maturation of BM-DCs pulsed with HPV11E7 CTL epitope peptide. In combination with the epitope peptide, the TLR agonists CPG and PIC augmented epitope-specific Th1 cytokine production in vivo, while imiquimod and CPG, but not PIC, enhanced Th1 cytokine production in vitro. However, we failed to observe in vivo CTL cytotoxicity and anti-tumour protection upon TLR ligation in our mouse model. Our results demonstrate that TLR agonists activate HPV11E7 CTL epitope pulsed BM-DCs to promote specific Th1 immunity in C57BL/6 mouse model, indicating the promise of TLR agonists as adjuvants for HPV epitope/DC-based multifaceted vaccines against HPV infections such as condyloma accuminatum.

Keywords: HPV - human papillomavirus; TLR - toll-like receptor; DC - dendritic cell

Published: December 31, 2011  Show citation