Changes of regulatory T cell number in hepatocellular carcinoma-bearing mice and its relationship with tumor growth.
- Author:
Pin ZHANG
1
;
Li-ning ZHANG
;
Fa-liang ZHU
;
Qun WANG
;
Xiao-yan WANG
;
Hai-yan LI
;
Chun-mei LIU
;
Fei GAO
;
Cheng-hu LIU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; CD4 Antigens; immunology; CD4-Positive T-Lymphocytes; cytology; immunology; metabolism; Cell Line, Tumor; Cell Proliferation; Female; Flow Cytometry; Forkhead Transcription Factors; genetics; metabolism; Gene Expression Regulation, Neoplastic; Interleukin-2 Receptor alpha Subunit; immunology; Liver Neoplasms; immunology; metabolism; pathology; Liver Neoplasms, Experimental; immunology; metabolism; pathology; Lymph Nodes; immunology; metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Reverse Transcriptase Polymerase Chain Reaction; Spleen; immunology; metabolism; T-Lymphocytes, Regulatory; cytology; immunology; metabolism
- From: Chinese Journal of Oncology 2007;29(5):342-345
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the relationship between the change of regulatory T cell number in CD4+ T subset and the growth of tumor in H22 hepatocellular carcinoma-bearing mice.
METHODSTumor-bearing mice were established by subcutaneous inoculation of H22 hepatocelluler carcinoma cells. Flow cytometry was used to detect the expression of CD4 and CD25 molecules of the T cells which came from the tumor-bearing mice. The Foxp3 gene expression was detected by RT-PCR and flow cytometry. CD4+ CD25+ T cells and CD4+ CD25- T cells were separated and purified by immuno-magnetic beads. The proliferation and suppressive function of the CD4+ CD25+ T cells coming from tumor-bearing mice was measured by [3H]-thymidines incorporation experiment in vitro, and then effect of CD4+ CD25+ T cells originated from hepatocellular carcinoma-bearing mice on tumor growth was observed in vivo.
RESULTS(1) Compared with mice of the control group, the percentage of CD4+ CD25+ T cells of CD4+ T cells in tumor-bearing mice is not only higher in draining lymph nodes (18.80% < or = 0.06%) vs. (9.50% +/- 0.03%), (P < 0.01), but also higher in non-draining lymph nodes (LN) and spleen (SP), LN: (16.28% +/- 0.02%) vs. (9.50% +/- 0.03%), P < 0.01; SP: (17.28% +/- 0.06%) vs. (11.08% +/- 0.04%), (P < 0.05). The expression of regulatory T cell specific marker Foxp3 gene was also increased. In the same tumor-bearing mice, the number of CD4+ CD25+ T cells in draining lymph node was relatively higher than the contralateral nondraining lymph node, but the difference was statistically not significant (18.8% +/- 0.06%) vs. (16.28% +/- 0.02%), (P > 0.05). (2) The CD4+ CD25+ T cells purified from tumor-bearing mice--like naturally occurring regulatory T cells--were anergic to anti-CD3 monoclonal antibody stimulation in vitro, but it could suppress CD4+ CD25- T cells proliferation. (3) The percentage of CD4+ CD25+ T cells was positively related to tumor size. It could also suppress the anti-tumor effect of CD4+ CD25- T cells in vivo. Conclusion The growth of hepatocellular carcinoma in mice can boost the amount of regulatory T cells. The amount of regulatory T cells is positively related to tumor size, indicating that attack on regulatory T cells could be used as one of modalities in cancer treatment in the future.
