title: Praziquantel facilitates IFN-γ-producing CD8+ T cells (Tc1) and IL-17-producing CD8+ T cells (Tc17) responses to DNA vaccination in mice.
abstract: BACKGROUND
  CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination.
  
  
  RESULTS
  Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+) T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8(+) T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+) T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes.
  
  
  CONCLUSIONS
  Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+) T cell-based immunotherapy that breaks tolerance to HBsAg.
authors: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors: Qiang
authors: Q
authors: Zou
authors: Xin
authors: X
authors: Yao
authors: Jin
authors: J
authors: Feng
authors: Zhinan
authors: Z
authors: Yin
authors: Richard
authors: R
authors: Flavell
authors: Yanxin
authors: Y
authors: Hu
authors: Guoxing
authors: G
authors: Zheng
authors: Jin
authors: J
authors: Jin
authors: Youmin
authors: Y
authors: Kang
authors: Bing
authors: B
authors: Wu
authors: Xiaoxuan
authors: X
authors: Liang
authors: Congcong
authors: C
authors: Feng
authors: Hu
authors: H
authors: Liu
authors: Weiyi
authors: W
authors: Li
authors: Xianzheng
authors: X
authors: Wang
authors: Yumei
authors: Y
authors: Wen
authors: Bin
authors: B
authors: Wang
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011223:Praziquantel / Q000494:pharmacology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D020381:Interleukin-17; D019444:Vaccines, DNA; D011223:Praziquantel; D007371:Interferon-gamma