Hong-Wei Wang, Min Zhang, Jie Luan, Wei-Jiang Hu, Ping Zhao, Jun Gao, Zhong-Tian Qi
{"title":"抗原表达重组鼠伤寒沙门菌在体内激活启动子驱动下能够在转基因小鼠中诱导细胞免疫应答。","authors":"Hong-Wei Wang, Min Zhang, Jie Luan, Wei-Jiang Hu, Ping Zhao, Jun Gao, Zhong-Tian Qi","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>To explore the approaches and mechanisms for reversing the immune tolerance in transgenic mouse, and the pathogenicity of hepatitis G virus (HGV), the promoter of phoP-activated gene (P(pagC)) of Salmonella typhimurium was used as a transcriptionally regulating element to construct an attenuated S. typhimurium expressing HGV NS3. The recombinant S. typhimurium was orally administered to HGV transgenic mice. As the results, HGV antigen in serum and liver as well as HGV mRNA in liver were decreased significantly, although the serum anti-HGV NS3 remained undetectable as the control transgenic mice. The spleen cell proliferation, in vitro HGV NS3 specific CTL, and IFN-gamma assays with the primed cultured splenocytes indicated the induction of Th1 immune responses in those administered transgenic mice. Adoptive transfer of fractionated primed spleen cells to the transgenic mice showed that T lymphocytes were responsible for, maybe through IFN-gamma, the down-regulation of HGV mRNA transcription. Histological examination found no significant inflammatory changes in liver of the transgenic mice. These findings suggested that the oral inoculation of the HGV NS3-expressed attenuated S. typhimurium driven by an in vivo-activated promoter should be a simple and effective approach for potential treatment of chronic viral infection.</p>","PeriodicalId":21763,"journal":{"name":"Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antigen-expressed recombinant Salmonella typhimurium driven by an in vivo-activated promoter is capable of inducing cellular immune response in transgenic mice.\",\"authors\":\"Hong-Wei Wang, Min Zhang, Jie Luan, Wei-Jiang Hu, Ping Zhao, Jun Gao, Zhong-Tian Qi\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>To explore the approaches and mechanisms for reversing the immune tolerance in transgenic mouse, and the pathogenicity of hepatitis G virus (HGV), the promoter of phoP-activated gene (P(pagC)) of Salmonella typhimurium was used as a transcriptionally regulating element to construct an attenuated S. typhimurium expressing HGV NS3. The recombinant S. typhimurium was orally administered to HGV transgenic mice. As the results, HGV antigen in serum and liver as well as HGV mRNA in liver were decreased significantly, although the serum anti-HGV NS3 remained undetectable as the control transgenic mice. The spleen cell proliferation, in vitro HGV NS3 specific CTL, and IFN-gamma assays with the primed cultured splenocytes indicated the induction of Th1 immune responses in those administered transgenic mice. Adoptive transfer of fractionated primed spleen cells to the transgenic mice showed that T lymphocytes were responsible for, maybe through IFN-gamma, the down-regulation of HGV mRNA transcription. Histological examination found no significant inflammatory changes in liver of the transgenic mice. These findings suggested that the oral inoculation of the HGV NS3-expressed attenuated S. typhimurium driven by an in vivo-activated promoter should be a simple and effective approach for potential treatment of chronic viral infection.</p>\",\"PeriodicalId\":21763,\"journal\":{\"name\":\"Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2003-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Antigen-expressed recombinant Salmonella typhimurium driven by an in vivo-activated promoter is capable of inducing cellular immune response in transgenic mice.
To explore the approaches and mechanisms for reversing the immune tolerance in transgenic mouse, and the pathogenicity of hepatitis G virus (HGV), the promoter of phoP-activated gene (P(pagC)) of Salmonella typhimurium was used as a transcriptionally regulating element to construct an attenuated S. typhimurium expressing HGV NS3. The recombinant S. typhimurium was orally administered to HGV transgenic mice. As the results, HGV antigen in serum and liver as well as HGV mRNA in liver were decreased significantly, although the serum anti-HGV NS3 remained undetectable as the control transgenic mice. The spleen cell proliferation, in vitro HGV NS3 specific CTL, and IFN-gamma assays with the primed cultured splenocytes indicated the induction of Th1 immune responses in those administered transgenic mice. Adoptive transfer of fractionated primed spleen cells to the transgenic mice showed that T lymphocytes were responsible for, maybe through IFN-gamma, the down-regulation of HGV mRNA transcription. Histological examination found no significant inflammatory changes in liver of the transgenic mice. These findings suggested that the oral inoculation of the HGV NS3-expressed attenuated S. typhimurium driven by an in vivo-activated promoter should be a simple and effective approach for potential treatment of chronic viral infection.