Hongyu Jia1, Chunling Li2, Yimin Zhang1, Liang Yu1, Dairong Xiang1, Jun Liu1, Fengzhe Chen3, Xiaochun Han4. 1. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, Zhejiang, China. 2. ICU of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Chengdu 610072, Sichuan, China. 3. Department of Infectious Diseases, Qilu Hospital of Shandong University Jinan 250013, Shandong, China. 4. Department of Preventive Medicine, Shandong University of Traditional Chinese Medicine Jinan 250355, Shandong, China.
Abstract
OBJECTIVE: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). METHODS: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. RESULTS: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. CONCLUSION: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection.
OBJECTIVE: This study is to investigate the immunostimulatory activities of dendritic cells (DCs) transfected with HBcAg and/or HBsAg recombinant adenovirus (rAd). METHODS: DCs were transfected with rAd (DC/Ad-C+Ad-S, DC/Ad-C, and DC/Ad-S), or pulsed with HBcAg antigen (DC/HBcAg). Flow cytometry was used to detect the phenotype of DCs and the cytokine production of T lymphocytes. Mice were vaccinated with DCs transfected with rAd or pulsed with antigen, and DNA vaccine. Mixed lymphocyte reaction (MLR) was used to evaluate the T-cell stimulatory capacity, and HBcAg-specific cytotoxic T lymphocyte (CTL) activity was assessed. RESULTS: Phenotypic analysis showed that DCs transfected with rAd or pulsed with HBcAg antigen exhibited mature phenotypes. MLR indicated no significant differences in stimulating T-cell proliferation between the DC/rAd and DC/HBcAg groups. When mixed with DCs, Th and Tc cells mainly secreted IFN-γ, indicating type I immune responses. In vaccinated mice, DCs transduced with rAd and pulsed with HBcAg induced significantly more IFN-γ secretion from Th cells, compared with DNA vaccine, indicating stronger Th1 response. Moreover, DCs transduced with rAd stimulated Tc cells to produce more IFN-γ, indicating stronger Tc1 response. In vaccinated mice, HBcAg-specific CTL activities were decreased in the following order: the DC/Ad-C+Ad-S, DC/Ad-C, DC/Ad-S, DC/HBcAg, and DNA vaccine groups. CONCLUSION: DCs transfected with rAd induce stronger Th1/Tc1 (type I) cell immune responses and specific CTL response than HBcAg-pulsed DCs or DNA vaccine. Our findings suggest that DCs transfected with rAd-C/rAd-S might provide an effective approach in the treatment of persistent hepatitis B virus infection.
Entities:
Keywords:
Hepatitis B core antigen (HBcAg); adenovirus; cytotoxic T lymphocytes; dendritic cells (DCs); hepatitis B surface antigen (HBsAg)
Authors: Monika C Wolkers; Nathalie Brouwenstijn; Arnold H Bakker; Mireille Toebes; Ton N M Schumacher Journal: Science Date: 2004-05-28 Impact factor: 47.728
Authors: J Heathcote; J McHutchison; S Lee; M Tong; K Benner; G Minuk; T Wright; J Fikes; B Livingston; A Sette; R Chestnut Journal: Hepatology Date: 1999-08 Impact factor: 17.425
Authors: A Bertoletti; F V Chisari; A Penna; S Guilhot; L Galati; G Missale; P Fowler; H J Schlicht; A Vitiello; R C Chesnut Journal: J Virol Date: 1993-04 Impact factor: 5.103
Authors: Benita L McVicker; Geoffrey M Thiele; Carol A Casey; Natalia A Osna; Dean J Tuma Journal: Int Immunopharmacol Date: 2013-03-26 Impact factor: 4.932