Praziquantel Facilitates IFN-γ-Producing CD8 T Cells Tc1 and IL-17-Producing CD8 T Cells Tc17 Responses to DNA Vaccination in MiceReport as inadecuate




Praziquantel Facilitates IFN-γ-Producing CD8 T Cells Tc1 and IL-17-Producing CD8 T Cells Tc17 Responses to DNA Vaccination in Mice - Download this document for free, or read online. Document in PDF available to download.

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.

Methodology-Principal Findings

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-Significance

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.



Author: Qiang Zou, Xin Yao, Jin Feng, Zhinan Yin, Richard Flavell, Yanxin Hu, Guoxing Zheng, Jin Jin, Youmin Kang, Bing Wu, Xiaoxuan Lian

Source: http://plos.srce.hr/



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