[Mechanism of enhancement of the CTL activity in mice co-expressing CD80, CD86 and CD137L genes].
OBJECTIVE
To study the mechanism of enhancement of the CTL activity in mice co-expressing of CD80, CD86 and CD137L genes.


METHODS
The mice were randomly divided into five groups, named A, B, C, D and E. The group A and B were control groups (CG). H22-BAL B/c HCC mouse model was established by subcutaneous injection with hepatocellular carcinoma cells of cell line H22-Wt (group A), H22-neo (group B), H22-CD80/CD86(+) (group C), H22-CD137L(+) (group D) and H22-CD80/CD86/CD137L(+) (group E), respectively. On the 14th, 35th, 56th and 84th day after the first inoculation of tumor cells, TUNEL staining and DNA ladder examination were used to detect apoptosis of splenic T lymphocytes in all groups at each post-inoculation time point. Electrophoretic mobility-shift assay (EMSA) method was used to detect the activity of nuclear factor kappaB (NF-kappaB) in splenic T lymphocytes in each group at each time point post-inoculation.


RESULTS
Apoptosis was found in a great number of T lymphocytes in CG on the 14th day, much more than that in group C and E. The number of apoptotic T cells in group C had a significant difference compared with that in the group E from 14th to 84th day (P = 0.003). DNA ladder analysis showed typical positive results in group C and E. The significant apoptosis fragments were found in group C on 21st, 35th and 84th days. NF-kappaB activity of T cells in groups C and E was remarkably higher than that of groups CG and D, with higher in group D than that of CG (P = 0.002), and with no significant difference between group C and E on 14th day. The activity in group E was stable and remarkably higher than that of group C on 56th and 84th days after the first inoculation.


CONCLUSIONS
H22-CD80/CD86/CD137L(+) induces higher NF-kappaB activity of the host T cells by synergistic action of CD28 and CD137, which may be one of the mechanisms of enhancement of the host CTL activity induced by co-expression of CD80, CD86 and CD137L genes.
Yin
Jie
J
Department of Respiratory Diseases, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China.
Li
Guo-Qiang
GQ
Yu
Yue
Y
Shi
Yi
Y
Sun
Bei-Cheng
BC
Cheng
Feng
F
Ge
Wen-Gang
WG
Wang
Xue-Hao
XH
D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism*; D051940:B7-2 Antigen / Q000378:metabolism*; D018106:CD28 Antigens; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D053330:4-1BB Ligand; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D016328:NF-kappa B