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Increased Frequency of Foxp3+ Regulatory T Cells in Mice with Hepatocellular Carcinoma

  • Du, Yong (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College) ;
  • Chen, Xin (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College) ;
  • Huang, Zhi-Ming (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College) ;
  • Ye, Xiao-Hua (Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College) ;
  • Niu, Qing (Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College)
  • Published : 2012.08.31

Abstract

The CD4+CD25+ regulatory T cell (Treg) is a special kind of T cell subset. Studies have showed that Treg cells are involved in a number of physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer. Tregs with unique capacity for immune inhibition can impair anti-tumour immunity and help tumor cells to escape from immune surveillance. The aim of our study was to investigate whether Tregs are involved in hepatocellular carcinoma (HCC). A BABL/C mouse with HCC in situ model was established to evaluate the Treg existence in carcinoma tissues and the changes of Tregs in spleen using flow cytometry and immunohistochemistry methods. Granzyme B expression in carcinoma tissues was analyzed by immunohistochemistry to investigate the tumor local immune status.The proportion of CD4+CD25+/CD4+ spleen lymphocytes of tumor bearing mice ($18.8%{\pm}1.26%$) was found to be significantly higher than that in normal mice ($9.99%{\pm}1.90%$) (P<0.01 ). Immunohistochemistry of spleen tissue also confirmed that there was an increase in Treg in tumor-bearing mice, while in carcinomas it showed Treg cells to be present in tumor infiltrating lymphocyte areas while Granzyme B was rarely observed. Anti-tumour immunity was suppressed, and this might be associated with the increase of Tregs. Our observations suggest that the CD4+CD25+Treg/CD4+ proportion in spleen lymphocytes can be a sensitive index to evaluate the change of Tregs in hepatocellular carcinoma mice and the Treg may be a promising therapeutic target for cancer.

Keywords

Hepatocellular carcinoma;regulatory T cell;CD4+CD25+ T cell;Foxp3;Granzyme B

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