树突状细胞诱导的细胞毒性T细胞对黑色素瘤的抑制作用

Inhibitory effects of cytotoxic T lymphocyte induced by dendritic cells on melanoma

目的探讨CIM^＋CD25^＋Treg细胞对树突状细胞（DC）诱导的细胞毒性T细胞（CTL）对B16黑色素瘤抑瘤作用的影响及其机制。方法制备C57BL/6小鼠B16黑色素瘤动物模型，行全身放疗达非髓性淋巴细胞删除（NMLD）状态。随机将80只小鼠分为4组。A组：在DC与T细胞共同培养前应用免疫磁珠法（MACS）删除CIM^＋CD25^＋Treg细胞；B组：DC与T细胞共同培养后删除CIM^＋CD25^＋Treg细胞；C组：DC与T细胞共同培养时不删除CIM^＋CD25^＋Treg细胞。D组：对照组。体外应用DC诱导T细胞产生效应细胞CTL，将CTL经鼠尾静脉回输小鼠体内，观察对黑色素瘤的抑瘤效果。结果A、B、c3组对B16黑色素瘤抑瘤率分别为90．89％、92．52％、60．02％，均明显高于对照组（P〈0．05）。删除CIM^＋CD25^＋Treg细胞的A、B两组抑瘤率优于C组（P〈0．05）。但A、B两组问抑瘤率差异无统计学意义（P〉0．05）。结论删除CIM^＋CD25^＋Treg细胞可明显提高CTL对B16黑色素瘤的抑瘤效果。

Objective To investigate the role of CD4 ＋ CD25 ＋ regulatm7 T cell （Treg） in cytotox- ic T lymphocyte （CTL） inhibiting B16 melanoma and the mechanism. Methods B16 melanoma cells were injected into subcutaneous tissue under the left shoulder of the C57BL/6 mouse to make the melanoma ani mal models. Then the animal models were irradiated by ^60Co-ray on the total body in order to get a no-mar row lymphocyte deletion （NMLD） state. Eighty C57BL/6 mice were divided into 4 groups： 3 experimental groups and a control group, with 20 mice each. In vitro T cells were induced into CTL with tumor specifici ty. CTL were injected back into the mouse body through the vein in the tail. The changes of tumor volume and tumor weight were observed. Results The tumor inhibition rate in the three experiment groups was 90. 89%, 92. 52% and 60. 02% respectively, which was significantly higher than that in the control group （P 〈0. 05）. A significant tumor inhibition was observed in groups A and B with a deletion of CD4 ＋ CD25 ＋ Tregs, in comparison with that in group C with no deletion of Tregs （ P 〈 0. 05 ）. But no significant difference was found between groups A and B with deletion of Tregs at different time points （ P 〉 0. 05 ）. Conclusion The deletion of CIM ＋ CD25 ＋ Treg could significantly increase the tumor inhibition effect of antigen-specific CTL in melanoma.