Archives of Dermatological Research

, Volume 302, Issue 1, pp 57–65

Toll like receptor agonists augment HPV 11 E7-specific T cell responses by modulating monocyte-derived dendritic cells

  • Xian-Zhen Chen
  • Xiao-Hong Mao
  • Ke-Jian Zhu
  • Na Jin
  • Jun Ye
  • Jian-Ping Cen
  • Qiang Zhou
  • Hao Cheng
Original Paper

DOI: 10.1007/s00403-009-0976-0

Cite this article as:
Chen, XZ., Mao, XH., Zhu, KJ. et al. Arch Dermatol Res (2010) 302: 57. doi:10.1007/s00403-009-0976-0

Abstract

Impaired local cellular immunity is one of the mechanisms responsible for condyloma acuminatum (CA) recurrence. The activation of dendritic cells (DCs) is important in vaccine development. We investigated the effect of different toll like receptor (TLR) agonists including LPS (TLR4 agonist), polyinosinic acid-polycytidylic acid (PIC, TLR3 agonist), CpG oligonucleotide (TLR9 agonist), and imiquimod (TLR7 agonist) on human monocyte-derived dendritic cells (mdDCs) loading of human papillomavirus (HPV) type 11 E7 epitope. As a result, we found that mdDCs loading HLA-A*0201-restricted HPV 11 E7 CTL epitope peptide could respond to the TLR agonists, especially LPS and PIC. This was characterized by an enhanced expression of CD40, CD80, CD86, CD83 and HLA-DR, and a high level of IL-12 production. TLR agonists, especially PIC, enhanced the ability of E7-loaded mdDCs to induce IFN-γ-secretion CD4+ naïve T cells. Moreover, E7-loaded mdDCs exposed to TLR agonists augmented autologous T cell responses including effector cytokines production and specific cytotoxic T lymphocyte (CTL) responses. In addition, the inhibitory effect of IL-10 on mdDCs maturation could be partially restored by LPS, PIC or imiquimod. Taken together, these results demonstrate that TLR agonists promoted the maturation of E7-loaded mdDCs and their ability to induce T help type 1 polarization and augment E7-specific T cell responses. These data also indicated that TLR3/4 agonists might be effective adjuvants of mdDC-based vaccines against CA.

Keywords

Human papillomavirus Condyloma acuminatum Toll like receptor Agonist Dendritic cells 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Xian-Zhen Chen
    • 1
  • Xiao-Hong Mao
    • 2
  • Ke-Jian Zhu
    • 1
  • Na Jin
    • 1
  • Jun Ye
    • 1
  • Jian-Ping Cen
    • 1
  • Qiang Zhou
    • 1
  • Hao Cheng
    • 1
  1. 1.Department of Dermatology and Venereology, Biomedical Research Center, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouPeople’s Republic of China
  2. 2.Department of Dermatology and Venereology, School of Medicine, The Second Affiliated HospitalZhejiang UniversityHangzhouPeople’s Republic of China