B7-H1阻断对CD3AK细胞体外生物学活性的影响

Effects of B7-H1 blockade on biologic activity of CD3AK cells in vitro

目的:探讨B7-H1阻断对CD3AK细胞增殖活化及其抗肿瘤免疫效应的影响。方法:利用CD3单克隆抗体(mAb)刺激健康人外周血淋巴细胞诱导产生CD3AK细胞,然后利用B7-H1阻断型抗体阻断B7-H1通路,3H-TdR渗入法检测阻断后CD3AK细胞的增殖能力,ELISA法检测阻断后CD3AK细胞分泌IFN-γ、TNF-α和IL-10的水平,同时将CD3AK细胞作用于膀胱肿瘤BIU-87细胞,MTT法检测阻断后CD3AK细胞的杀伤活性。结果:B7-H1阻断后,CD3AK细胞的增殖能力明显增强,体外存活时间明显延长;其分泌IFN-γ、TNF-α的水平明显提高,而分泌IL-10的水平明显下降;同时CD3AK细胞对BIU-87细胞的杀伤活性亦明显升高。结论:阻断B7-H1通路可以促进和维持CD3AK细胞的增殖和活化,并增强其抗肿瘤的免疫效应。阻断B7-H1通路将有望成为肿瘤免疫治疗的新策略。

AIM： To investigate the effect of B7-H1 blockade on proliferation, activation, and antitumor immuni- ty of CD3AK cells. METHODS： CD3AK cells were induced by stimulation of normal human peripheral blood lymphocytes with CD3 mAbs. Then the cells were cultured with anti-B7-H1 mAbs to block B？-H1 pathway. The proliferation ef- ficiency of CD3AK cells was measured by ^3H-thymidine incorporation assay and the concentrations of IFN-γ, TNF-α and IL-10 were measured by ELISA method. Meanwhile the killing activity of CD3AK cells on bladder cancer cell line BIU-87 was measured by MTT method. RESULTS： Blockade of B7-H1 greatly promoted the proliferation of CD3AK cells and extended the survival time of CD3AK cells in vitro. It also enhanced IFN-γ, TNF-α secretion but suppressed IL- 10 secretion. And the cytotoxic effect of CD3AK cells on BIU-87 cells were significantly enhanced. CONCLUSION： Blockade of B7-H1 can promote and retain the proliferation and activation of CD3AK cells. It can also improve the antitumor immunity mediated by CD3AK cells. The manipulation of B7-H1 may become a beneficial target for immunotherapy in tumors.