title: Toll like receptor agonists augment HPV 11 E7-specific T cell responses by modulating monocyte-derived dendritic cells.
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-gamma-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.
authors: Department of Dermatology and Venereology, Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 East Qingchun Road, 310016 Hangzhou, Zhejiang, People's Republic of China.
authors: Xian-Zhen
authors: XZ
authors: Chen
authors: Xiao-Hong
authors: XH
authors: Mao
authors: Ke-Jian
authors: KJ
authors: Zhu
authors: Na
authors: N
authors: Jin
authors: Jun
authors: J
authors: Ye
authors: Jian-Ping
authors: JP
authors: Cen
authors: Qiang
authors: Q
authors: Zhou
authors: Hao
authors: H
authors: Cheng
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D017951:Antigen Presentation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000209:etiology* / Q000517:prevention & control; D003218:Condylomata Acuminata; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D052140:Human papillomavirus 11 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D000077271:Imiquimod; D007371:Interferon-gamma / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000473:pathology; D009841:Oligonucleotides / Q000494:pharmacology; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051193:Toll-Like Receptors / Q000819:agonists*; D014412:Tumor Virus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002583:Uterine Cervical Neoplasms / Q000209:etiology* / Q000517:prevention & control; D014765:Viral Vaccines
chemical_list: D000634:Aminoquinolines; C493190:E7 protein, human papillomavirus 11; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008070:Lipopolysaccharides; D009841:Oligonucleotides; D009856:Oncogene Proteins, Viral; D051193:Toll-Like Receptors; D014765:Viral Vaccines; D007371:Interferon-gamma; D011070:Poly I-C; D000077271:Imiquimod