U14-CBE脂质体瘤苗诱导的细胞和体液免疫应答

Cellular and humoral immune responses to cervix carcinoma in mice induced by liposomal crude butanol extraction(CBE)-based vaccine

目的探讨脂质体瘤苗诱导的免疫应答,以探明细胞表面抗原(crude butanol extraction,CBE)-脂质体瘤苗诱导抗癌免疫的效应机制。方法采用正丁醇法提取子宫颈癌U14-CBE,以卵磷脂(ePC)、磷脂酰乙醇胺(PE)和胆固醇(Chol)制成大单层脂质体,将CBE包裹入脂质体,制成CBE-脂质体瘤苗。分别于第0、7、14天将CBE-脂质体瘤苗腹腔接种于免疫Km小鼠体内,在免疫后的第7、14、24天处死小鼠,取组织称湿重,并行组织学、组织化学观察脾脏中由该脂质体瘤苗诱导的T细胞和B细胞的反应。结果经U14-CBE脂质体和单纯CBE免疫的小鼠脾脏重量明显高于空白对照组和空白脂质体组(P<0.05),且CBE脂质体组脾重呈持续性增长,而单纯CBE组脾重于第14天达高峰,第24天又有所回落。组织学和组织化学染色显示脾脏中细动脉周围淋巴鞘(periarterial lymphatic sheath,PALS)和免疫母细胞数量增多、嗜派若宁大细胞增多以及淋巴小结增多、生发中心活性加强和浆细胞数量增多。结论 CBE-脂质体瘤苗既可引起显著的细胞免疫反应,也可引发体液免疫反应。

Purpose To study the immune response induced by CBE-liposomal vaccine and to explore the effect mechanism of antiean- cer immune induced by CBE-liposomal vaccine. Methods In this experiment the crude butanol extraction of Ul4 （UI4-CBE） was pre- pared by 1-butanol, and liposomal made up of ePC, PE and Chol were producted. The liposmal vaccine encapsulating UI4-CBE was prepared by a method of combinating of the thin-film hydration, ultrasonication and extrusion through polyearbonate fliters. The Km mice were immunized i. p （ intraperitoneal injection） on day 1, day 7 and day 14. A group of mice were killed for taking fresh spleens to be observed on day 7, day 14 and day 24 resspectively. The spleens were wet weight, then observed to determine the T and B cell immune responses resulting from liposomal vaccine encapsulating UI4-CBE inducing by using histology, histochemistry and immunohis- tochemistry methods. Results The splenic weight of the mice immunized with U14-CBE liposomal vaccine and pure CBE were higher than those in blank control and blank liposomal group （P 〈0.05）. Moreover, the splenic weight of mice in CBE liposomal group was increasing, but the splenic weight of mice in pure CBE group arrived at peak on day 14 and returned on day 24. The histological and histochemical observations on lymphoid tissue of immunized mice showed that the number of periarterial lymphatic sheath （PALS） , im- munoblasts, large pyroninophilic lymphoid cells and germinal centers was increased, lymphocytic germinal center＇ s activity was rein- forced, and the number of plasmcoyte in the spleen was also increased. Conclusions The study indicated that liposome, when encap- sulated tumor antigen, can improve the immunogenicity of this antigen. Liposomal antigen-based vaccine could elicit the significant cel- lular and humoral immune response in mice.