title: Tumor-derived CD4+CD25+regulatory T cells inhibit dendritic cells function by CTLA-4.
abstract: OBJECTIVE
  CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way. However the mechanism of how HCC-derived Treg affect DC phenotype are not very clear. Therefore, we investigated the function of CTLA-4 in anti-tumor immune responses.
  
  
  METHODS
  We established BABL/C mouse with hepatocellular carcinoma model, and tumor-derived Tregs were purified by magnetic cell sorting using mouse CD4+CD25+regulatoryT cell isolation kit. Splenic DCs were enriched using CD11c-conjugated microbeads. Then splenic DCs co-cultured with tumor-derived Tregs and antibody-blocking experiments was performed.
  
  
  RESULTS
  In our research, we found the down-modulation of CD80/CD86 on DCs was inhibited by blocking CTLA-4. HCC-derived Tregs down-modulated CD80/CD86 on DCs in a CTLA-4-dependent way. Blockade of CTLA-4 can lead to increase DC-mediated immunity.
  
  
  CONCLUSIONS
  CTLA-4 play a vital role in Treg-mediated immnue inhibition and this discovery can open up new ideas for the development of therapeutic strategies.
authors.affiliation: Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, ZheJiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, ZheJiang, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China. Electronic address: 515359290@qq.com.
authors.forename: ZhiMing
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003713:Dendritic Cells / Q000378:metabolism*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D060908:CTLA-4 Antigen
keywords: CD4+CD25+regulatory T cell; CTLA-4; Dendritic cell