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题名:Hepatocellular carcinoma cell supernatants increase expansion and function of CD4(+)CD25(+) regulatory T cells.
作者:Cao M, Cabrera R, Xu Y, Firpi R, Zhu H, Liu C, Nelson DR. Related Articles, Links
来源:Lab Invest[IF=3.859]. 2007 Mar 19; [Epub ahead of print]
URL :http://dx.doi.org/10.1038/labinvest.3700540
日期:070415
摘要: Mengde Cao1,*, Roniel Cabrera1,*, Yiling Xu1, Roberto Firpi1, Haizhen Zhu1, Chen Liu1 and David R Nelson1

1Section of Hepatobiliary Diseases, Department of Medicine, University of Florida, Gainesville, FL, USA

Correspondence: Dr R Cabrera, MD, Section of Hepatobiliary Diseases, Department of Medicine, University of Florida, 1600 SW Archer Rd., PO Box 100214, Gainesville, FL 32610-0214, USA. E-mail: cabrer@medicine.ufl.edu

*These authors contributed equally to this work.

Received 24 November 2006; Revised 24 January 2007; Accepted 30 January 2007; Published online 19 March 2007.

Abstract

Dysfunction of the host immune system in cancer patients can be due to a number of factors, including suppression of tumor-associated antigen reactive lymphocytes by CD4+CD25+ regulatory T (Treg) cells. Several studies suggest that Tregs are elevated in cancer patients and that depletion of Tregs may enhance the antitumor immunity of host, but the pathogenic and mechanistic relationship between cancer and Tregs is still unclear. In this report, we show that Tregs are increased in peripheral blood mononuclear cells (PBMCs) from hepatocellular carcinoma (HCC) patients and positively correlate with tumor burden. When PBMCs are co-cultured with human hepatoma cell lines Huh7, HepG2, and Hclone5, CD4+CD25+-T cell populations increase in frequency and undergo phenotypic and functional changes. CD45RA, CD45RO, CD69, CD62L, GITR, CTLA-4, Ki67, granzyme A, granzyme B, and FOXP3 expression were upregulated in CD4+CD25+ cells after in vitro exposure to HCC cell lines. CD4+CD25+ T cells from PBMCs that were co-cultured with Huh7 cells also have higher suppressor ability compared to that of the CD4+CD25+ T cells from control PBMC. Huh7 culture supernatants appear to promote CD4+CD25+ T-cell proliferation and inhibit CD4+CD25- T-cell proliferation. In conclusion, these results strongly suggest that tumor-related factors not only induce and expand CD4+CD25+ cells, but also enhance their suppressor ability.

Keywords: hepatocellular carcinoma, PBMC, regulatory T cells, CD4+CD25+ T cells, Huh7, FOXP3 5:

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