B7-H4对宫颈癌患者外周血活化T细胞增殖、凋亡和分泌细胞因子的影响

目的：观察重组人 B7-H4蛋白对宫颈癌患者外周血 T 细胞增殖周期、凋亡及分泌细胞因子的影响。方法B7-H4分别与15例宫颈癌患者外周血活化淋巴细胞混合培养48 h 后,采用流式细胞术分析 T 细胞增殖、细胞周期、凋亡及各亚群 T 细胞的变化,酶联免疫吸附试验(ELISA)芯片检测培养上清液细胞因子含量。结果宫颈癌患者外周血 T 细胞与 B7-H4混合培养48 h 后,G1、G2和 S 期的 T 细胞分别占90.59%、8.55%和0.87%,空白对照组 T 细胞各期占92.83%、6.09%和1.13%；B7-H4组 CD4+ T 和 CD8+ T 细胞的 Ki67阳性率分别为2.13%±0.13%和1.03%±1.33%,空白对照组为2.74%±0.98%和1.71%±1.32%。B7-H4组较空白对照组 CD8+ T 和 CD4+ T 细胞占 T 细胞的比例下降,但 CD4+ T/CD8+ T 比值增高,CD4+ CD25+Foxp3+ T 细胞增多；B7-H4组混合培养上清液中 TGF-β1含量为(259.25±32.78)pg/mL,空白对照组为(202.75±20.17)pg/mL。B7-H4对宫颈癌患者外周血活化 T 细胞凋亡无明显影响。结论B7-H4使宫颈癌患者外周血活化 T 细胞被阻滞于 G2期, S 期细胞明显减少；B7-H4抑制 CD4+ T 和 CD8+ T 细胞增殖,但对 Foxp3+ T 细胞增殖和分泌 TGF-β1可能有促进作用；B7-H4对T 细胞凋亡无明显影响。B7-H4在抑制宫颈癌抗肿瘤细胞免疫中发挥作用,它可能成为宫颈癌免疫治疗的潜在靶点。

Influence of B7-H4 on cell proliferation,apoptosis and cytokine secretion of peripheral blood activated T cells in cervical cancer patients

Objective To observe the in vitro influence of recombinant human B7-H4 protein on the cell proliferation cycle, apoptosis and cytokine secretion of peripheral blood activated T lymphocytes in cervical cancer patients.Methods After 48 h co-culture of peripheral blood T lymphocytes in 1 5 cases of cervical cancer with B7-H4 48 h,T lymphocytes′cell proliferation cycle, apoptosis and T lymphocytes subtypes changes were detected by FCM;the cytokines concentration in the culture supernatant was tested by ELISA array.Results After 48 h co-culture of peripheral blood T lymphocytes with B7-H4 48hs,G1,G2 and S phase of T cells accounted for 90.59%,8.55% and 0.87% respectively,which of the blank group were 92.83%,6.09% and 1.13% respec-tively;the Ki67 positive rates of CD4 + T and CD8 + T cells in the B7-H4 group were 2.13%±0.13% and 1.03%±1.33% respec-tively,which of the blank group were 2.74% ±0.98% and 1.71% ± 1.32% respectively;the proportion of CD4 + T and CD8 + T cells accounting for T cells in the B7-H4 group was decreased compared with the blank group,but the ratio of CD4 + T/CD8 + T and the proportion of CD4 + CD25 + Foxp3 + T cells were increased,in addition,the TGF-β1 secretion;concentration in the co-culture su-pernatant in the B7-H4 group was (259.25±32.78)pg/mL,which was higher than (202.75 ±20.1 7)pg/mL in the blank group. B7-H4 had no significant influence on the peripheral blood activated T cells apoptosis.Conclusion B7-H4 block the peripheral blood activated T cells at G2 phase,the S phase cells are obviously decreased;B7-H4 inhibits the cellular proliferation of CD4 + T and CD8 + cells,but may have the promoting effect on Foxp3 + T proliferation and TGF-β1 secretion;B7-H4 has no significant influ-ence on T cell apoptosis.B7-H4 plays a role in depressing anti-tumor T cell immune response of cervical cancer and may become a potential target of cervical cancer immunotherapy.