Hsp70-p53合成肽修饰树突状细胞诱导细胞免疫应答的研究
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摘要
目的:研究Hsp70-p53合成肽复合物修饰的树突状细胞(DC)诱导的细胞免疫应答。方法:人工合成p53蛋白多肽,在体外与热休克蛋白Hsp70结合形成Hsp70-p53合成肽复合物后,修饰DC,以肿瘤细胞抗原肽作对照,刺激健康人外周血T淋巴细胞。检测增殖活化的T细胞对肿瘤细胞的杀伤功能及细胞因子表达水平。结果:Hsp70-p53合成肽复合物可促进DC成熟,分泌大量IL-12等细胞因子;并可刺激异体T淋巴细胞增殖,与单纯DC组比较有极显著差异(P<0.01);修饰的DC活化T细胞与单纯肿瘤抗原肽组对BEL-7402肝癌细胞杀伤作用无显著差异(P>0.05),而对7901胃癌细胞有差异(P<0.05)。结论:Hsp70-p53合成肽复合物能够修饰DC使其活化,激活T淋巴细胞,对高效表达突变型p53蛋白的肿瘤细胞株产生有效的杀伤作用。
Objective:To study the cellular immune response induced by Hsp70- p53 synthesized peptide complex- modified dendritic cells(DC).Methods:The p53_(W) as synthesized and bound Hsp70 in vitro:with DCs modified by Hsp70- p53 peptide or tumor antigen peptides.The proportion of stimulated T cells and The cytolytic effect of those activated T cells on cancer cells was tested.The expression oi cytokines in the T cells were examined.Results:The DCs could be activated and expressed large amount of IL- 12 by Hsp70- p53 peptide complex,there was significant difference between Hsp70- p53 and tumor antigen(P <0.01).T cell could be stimulated and proliferated by Hsp70- p53- modified DCs.There was significant difference between T cells stimulated with DCs and Hsp70- p53- modified DCs(P < 0.01).There was no significant difference between cytolytic effects of T cells activated with Hsp70- p53- modified DCs and tumor antigen- treated DCs(P >0.05) on BEL-7402 cells,while there was significant difference between that with Hsp70- p53- modified DCs and tumor antigen-treated DCs(P<0.05) on 7901 cells.Conclusion:DCs could be modified effectively by Hsp- p53 synthesized peptide-complexes.The modified DCs could activated specific T lymphocytes in vitro.
引文
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