流感疫苗促进髓系白血病骨髓细胞来源树突状细胞的功能  

Influenza vaccine enhances function of dendritic cells derived from bone marrow of patients with myeloid leukemia

作　　者：曾鹏云[1] 杜昊 张连生[1] 柴晔[1] 刘瑛[1] 

机构地区：[1]兰州大学第二医院血液科,甘肃兰州730030 [2]廊坊中医院血液科,河北廊坊065000

出　　处：《中国肿瘤生物治疗杂志》2009年第3期221-226,共6页Chinese Journal of Cancer Biotherapy

基　　金：甘肃省科学基金资助项目(No.0709TCYA063)~~

摘　　要：目的:研究流感疫苗对髓系白血病骨髓源性树突状细胞(dendritic cells,DCs)功能的影响及其机制。方法:分离髓系白血病患者[急性髓细胞白血病(acute myeloid leukemia,AML)19例,慢性髓细胞白血病(chronic myeloid leukemia,CML)8例]骨髓单个核细胞(mononuclear cell,MNC),用GM-CSF和IL-4诱导7d,获得未成熟白血病DCs,然后加入全病毒灭活流感疫苗(whole inactivated influenza vaccine,WIV)、裂解病毒流感疫苗(split influenza vaccine,SIV)或TNF-α继续培养24h。R显带法分析DCs染色体核型,流式细胞仪检测DCs表型,ELISA法测定DCs培养上清IL-12的水平,CCK8法检测DCs诱导的CTL对自体白血病细胞的细胞毒作用。结果:19例AML患者中的15例及8例CML患者的MNC全部成功诱导出DCs。与TNF-α刺激的白血病DCs相比,流感疫苗刺激的白血病DCs表面分子(CD80、CD83、CD86、HLA-DR)表达明显上调(P<0.05),培养上清中IL-12的分泌水平明显增加(P<0.05),其诱导的CTL可显著杀伤自体白血病细胞(P<0.05);WIV刺激的DCs在表型、IL-12分泌水平及细胞毒作用方面均较SIV刺激的DCs显著增高(P<0.05)。结论:流感疫苗促进髓系白血病源DCs表型成熟及IL-12的分泌,增强其诱导的CTL对自体白血病细胞的杀伤作用。Objective： To determine whether the influenza vaccine can affect the function of dendritic cells （DCs） derived from the bone marrow of patients with myeloid leukemia and the possible mechanism. Methods： The bone marrow （BM） mononuclear cells were obtained from 19 patients with acute myelocytic leukemia （AML） and 8 patients with chronic myeloid leukemia （CML） , and were cultured with GM-CSF and IL-4 for 7 days to obtain immature DCs. Then DCs were stimulated by whole inactivated influenza vaccine （ WIV）, split influenza vaccine （ SIV）, or TNF-α. After 24 h, phenotypes and karyotypes of these DCs were assessed by FACS and R band karyotype analysis, respectively. The supernatant IL-12 levels were measured by ELISA in each group. Cytotoxic activity of CTL induced by differently treated DCs was measured by CCK8 assay. Results： DCs were successfully induced in 15 of the 19 AML patients and all the 8 CML patients. After stimulated with WIV or SIV for 24 h, DCs exhibited enhanced expression of CD83, CD86 and HLA-DR, and increased secretion of IL-12 （all P 〈 0.05）. CTL induced by WIV- or SIV-stimulated DCs specifically killed autologous leukemia cells in vitro （ P 〈 0.05 ）. Furthermore, WIV-stimulated DCs were more powerful than SIV-stimulated DCs in killing target cells （P 〈 0.05 ）. Conclusion： Influenza vaccine can promote the maturation and IL-12 secretion of DCs derived from myeloid leukemia patients, and CTL induced by influenza vaccine-stimulated DCs has a stronger ability to kill autologous leukemia cells.

关 键 词：流感疫苗 树突状细胞 髓系白血病 细胞毒性T淋巴细胞 

分 类 号：R733.7[医药卫生—肿瘤] R392.7[医药卫生—临床医学]