[Development of HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and its immunological features].
OBJECTIVE
To develop a HPV16 positive cervical cancer model in the hu-PBL-SCID mouse and investigate its immunological features.


METHODS
Thirty-two CB17SCID mice were randomly divided into 4 groups: group A (5 mice) subcutaneously injected with phosphate-buffered saline, group B (5 mice) intraperitoneally injected with human peripheral blood lymphocyte (PBL) for immune reconstruction, group C (11 mice) subcutaneously injected with human cervical carcinoma cell line SiHa, and group D (11 mice) intraperitoneally injected with PBL and subcutaneously injected with SiHa cells after 24 hours of PBL transplantation. The tumor growth, behaviors and status of xenogeneic graft versus host disease (XGVHD) were observed. Human immunoglobulins G (IgG) in mouse serum, the percentage of human CD3(+), CD4(+) and CD8(+) T cells in peripheral blood and spleen, spleen weight, tumor infiltrating lymphocytes and human CD4(+) T cells, and cytotoxicity test of spleen cells were detected.


RESULTS
The rate of successful tumor transplantation was 100%. XGVHD was not found. On the 5th day, human IgG level in the group B (0.98 microg/ml +/- 0.20 microg/ml) and group D (1.39 microg/ml +/- 0.25 microg/ml) was significantly higher than that in the group A (t = 7.655, 9.937, both P = 0.000). Human IgG level in group D was significantly higher than that in the group B (t = 3.200, P = 0.006). Only very low levels of human serumal IgG were detected in the group C and group A with no significantly difference. The level of human serumal IgG was gradually elevated in all the humanized SCID mice as the the time after PBL transplantation went on, and was significantly higher than that in non-humanized mice (P < 0.05). The percentage of human CD3(+), CD4(+) and CD8(+) T cells was significantly increased in the peripheral blood and spleen of immunoreconstituted SCID mice. The weight of spleen was markedly increased in the group D. TIL infiltrating in the tumor were remarkable and human CD4(+) T cells was detected by immunohistochemistry in the group D but not in the group C. The spleen cells in the group D displayed stronger cytotoxicity to the target cells (P < 0.05).


CONCLUSIONS
Human immune function can be successfully reconstructed in SCID mouse via intraperitoneally injecting with human PBL, and induce anti-tumor immune response to the transplantated tumor of HPV16 positive cervical cancer.
Liang
Zhao-Xia
ZX
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
Cheng
Qi
Q
Chen
Huai-Zeng
HZ
Xie
Xing
X
Ye
Da-Feng
DF
D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000302:isolation & purification; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology*; D011897:Random Allocation; D016511:Severe Combined Immunodeficiency / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16