过继肿瘤特异性淋巴细胞联合mIL-21瘤苗抗肿瘤效应研究  

Anti-tumor mechanisms of lymphopenic mice transferred with tumor-specific lymphocytes and immunized with mIL-21 tumor vaccine

作　　者：吴昀[1] 刘春生[1] 窦骏[1] 赵枫姝[1] 胡卫华[1] 文萍[1] 胡凯[1] 何向峰[1] 

机构地区：[1]东南大学医学院病原微生物与免疫学系,南京210009

出　　处：《中华微生物学和免疫学杂志》2008年第12期1143-1148,共6页Chinese Journal of Microbiology and Immunology

基　　金：江苏省六大人才高峰资助项目（D14）

摘　　要：目的在环磷酰胺（Cy）所致小鼠淋巴细胞急剧减少状态下，过继mIL-21转染的瘤苗细胞（mIL-21-Sp2／0）免疫致敏的同系小鼠淋巴细胞，联合mIL-21-Sp2／0瘤苗免疫，探讨过继免疫抗瘤效应机制。方法用Cy100mg／kg预处理BALB／c小鼠2d后，以灭活mIL-21瘤苗免疫的同系小鼠脾及淋巴结的淋巴细胞作为肿瘤抗原特异性淋巴细胞过继给Cy预处理鼠，同时用mIL-21瘤苗免疫，7d后以野生型Sp2／0细胞攻击，观察小鼠的肿瘤生长情况。流式细胞仪（FCM）分析CD4^＋、CD8^＋、CD4^＋CD25^＋T细胞等亚群的变化，分别以CFSE和7-AAD标记，FCM检测淋巴细胞增殖能力和效应细胞的细胞毒活性，用ELISPOT检测分泌IFN-γ的淋巴细胞数量。结果与对照组相比，Cy预处理小鼠接受过继效应细胞及MIL-21瘤苗免疫后，可有效地抵抗野生型Sp2／0细胞的攻击。过继的肿瘤特异性淋巴细胞的体内增殖能力和体外杀伤活性显著增强，分泌IFN-γ效应细胞的数量显著增高。结论在小鼠淋巴细胞减少期，过继mIL-21瘤苗免疫致敏的肿瘤抗原特异性淋巴细胞并同时给予mIL-21瘤苗免疫，利于输入的效应细胞及自身免疫细胞的增殖和特异性抗肿瘤功能的形成与维持。Objective To explore the mechanism of anti-tumor effects of transferring tumor-specific lymphocytes obtained from pre-immunized BALB/e mice with inactive mIL-21 tumor vaccine （mIL-21- Sp2/0） to syngeneie mice, associated with mlL-21 tumor vaccine immunization, in the condition of eyclophosphamide （Cy） -induced lymphopenia. Methods Activated lymphocytes of spleen and lymph nodes ob- tained from pre-immunized syngeneic mice with irradiated mIL-21-Sp2/0 cells were infused into BALB/c mice treated with Cy 2 days before, subsequently vaccinated with mIL-21 tumor vaccine, after 7 days, challenged with Sp2/0 tumor cells, observed the growth of tumor of mice. T lymphocyte subsets differentiation was measured by flow cytometry （FCM） analysis. The proliferation and eytotoxic activities of activated lym- phocytes were analyzed by FCM, respectively, staining with CFSE and 7-AAD. The number of IFN-γ-secreting cells was evaluated by ELISPOT. Results The lymphopenic mice were transferred with activated lym-phocytes and inoculated with mlL-21 tumor vaccine might provide superior anti-tumor immunoprotection, retard tumor growth of the mice. The proliferating capabilities and killing rate of transferred tumor Ag-specifie lymphoeytes enhanced obviously, the number of IFN-γ-secreting cells was significantly higher compared with the control groups. Conclusion Under Cy-induced lymphopenia condition, tumor Ag-specific lymphocytes sensitized by raiL-21 tumor vaccine were transferred to mice and immunized with raiL-21 tumor vaccine at the same time, benefit the proliferation of transferred effective cells and immune cells itself, assist to form and sustain special anti-tumor effects.

关 键 词：mIL-21瘤苗 过继免疫治疗 自稳增殖 抗肿瘤作用 

分 类 号：R730.5[医药卫生—肿瘤]