Mechanism of enhancement of the CTL activity in mice co-expressing CD80, CD86 and CD137L genes / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To study the mechanism of enhancement of the CTL activity in mice co-expressing of CD80, CD86 and CD137L genes.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>