Sun Hua-Wen, Tang Qi-Bing, Tang Chong, Zou Sheng-Quan
Department of General Surgery, Renmin Hospital, Wuhan University, Wuhan 430060, China.
Hepatobiliary Pancreat Dis Int. 2005 Feb;4(1):121-5.
Dendritic cells (DCs) are the most potent antigen-presenting cells and are actively used in cancer immunotherapy. Wild-type p53 can be recognized as an antigen and can induce specific cytotoxic T lymphocytes (CTLs) in the host body. The aim of this study was to investigate the effects of DCs transfected with full length wild-type p53 and modified by bile duct lysates on immune response.
The wild-type p53 was transducted to DCs with adenovirus, which were modified by bile duct lysates (Lywtp53DC). The concentration of the surface molecules (B7-1, B7-2, MHC-I, MHC-II) of all DCs was detected with fluorescence activated cell sorter (FACS), and the ability of the DCs to induce efficient and specific immunological response in anti-(51)Cr-labeled target cells was studied. BALB/c mice infected with the DCs and QBC939 were used. CTL response in mice immunized with Lywtp53DC and treatment of tumor-bearing mice with Lywtp53DC and CTL response in these mice were studied.
The surface molecules of Lywtp53DC had a high expression B7-1 (86.70%+/-0.07%), B7-2 (18.77%+/-0.08%), MHC-I(87.20%+/-0.05%), MHC-II(56.70%+/-0.07%) with FACS. The T lymphocytes had a specific CTL lysing ability induced by Lywtp53DC, with a CTL lysis rate of 81%. The immune protection of Lywtp53DC group was obvious, and the tumor diameter of the Lywtp53DC group was 3.10+/-0.31 mm, 2.73+/-0.23 mm, 3.70+/-0.07 mm on days 13, 16 and 19, smaller than those of any control groups (P<0.05), DC, wtp53DC and LyDC. On the other hand, the growth rate of tumor of the Lywtp53DC group was slower than that of any other groups (P<0.05).
Dendritic cells transfected with wild-type p53 and modified by bile duct lysates have specific CTL killing capability.
树突状细胞（DCs）是最有效的抗原呈递细胞，被积极应用于癌症免疫治疗。野生型p53可被识别为一种抗原，并能在宿主体内诱导特异性细胞毒性T淋巴细胞（CTLs）。本研究旨在探讨经全长野生型p53转染并用胆管裂解物修饰的DCs对免疫反应的影响。
用腺病毒将野生型p53转导至DCs，并用胆管裂解物对其进行修饰（Lywtp53DC）。用荧光激活细胞分选仪（FACS）检测所有DCs表面分子（B7-1、B7-2、MHC-I、MHC-II）的浓度，并研究DCs在抗（51）Cr标记靶细胞中诱导高效特异性免疫反应的能力。使用感染了DCs和QBC939的BALB/c小鼠。研究了用Lywtp53DC免疫的小鼠的CTL反应以及用Lywtp53DC治疗荷瘤小鼠及其CTL反应。
FACS检测显示，Lywtp53DC的表面分子B7-1（86.70%±0.07%）、B7-2（18.77%±0.08%）、MHC-I（87.20%±0.05%）、MHC-II（56.70%±0.07%）有高表达。Lywtp53DC诱导的T淋巴细胞具有特异性CTL杀伤能力，CTL裂解率为81%。Lywtp53DC组的免疫保护作用明显，在第13、16和19天，Lywtp53DC组的肿瘤直径分别为3.10±0.31mm、2.73±0.23mm、3.70±0.07mm，小于任何对照组（P<0.05），即DC、wtp53DC和LyDC组。另一方面，Lywtp53DC组肿瘤的生长速度比其他任何组都慢（P<0.05）。
经野生型p53转染并用胆管裂解物修饰的树突状细胞具有特异性CTL杀伤能力。
