目的:探讨不同的免疫途径对抗原肽修饰树突状细胞(DC)疫苗免疫效果的影响。方法:用鸡卵清蛋白(OVA)MHCI限制性多肽SIINFEKL(OVAp257-264)包被小鼠骨髓来源的DC,通过皮下、腹腔、静脉或肌肉注射免疫小鼠,7天后行体内细胞毒性T淋巴细胞杀伤实验(InvivoCTL)分析CTL杀伤活性和细胞内IFN-γ染色(ICS)分析免疫小鼠脾脏CD8^+细胞产生IFN-γ的情况。结果:免疫7天后,InvlvoCTL结果显示SIINFEKL修饰的DC皮下、腹腔、静脉或肌肉注射免疫小鼠其特异性CTL杀伤效应分别是37.3%±7.3%、61.0%±4.2%、56.9%±3.6%和10.8%±2.3%;ICS结果示四组小鼠产生IFN-γ的CD8^+细胞占总CD8^+细胞的比例分别是0.31%±0.07%、0.85%±0.12%、0.76%±0.14%和0.15%±0.04%。结论:不同免疫途径可明显影响抗原肽修饰DC疫苗的免疫效应,其中腹腔注射诱发的抗原特异性CTL反应最强,静脉注射者次之,而皮下注射特别是肌肉注射较弱,提示通过腹腔注射DC疫苗可能是安全、高效的免疫途径。
Objective:To investigate the influence of different routes of administration on vaccine efficiency of peptide-pulsed dendritic cells(DC). Methods: Immunization of syngeneic C57BL/6 mice with bone marrow-derived murine DC pulsed with SIINFEKL, a MHC class I -restricted peptide from chicken ovalbumin(OVA) sited at 257-264 amino acid residuals were performed via subcutaneous( s. c. ) , intramuscular( i. m. ) , intravenous( i. v. ) , and intraperitoneal( i. p. ) administration, respectively. Seven days later the mice were sacrificed and the splenocytes were prepared to analyze antigen-specific CTL lysis for target cells and IFN-γ-produeting CD8^+T lymphocytes using in vivo CTL assay and intraceUular cytokine staining(ICS) , respectively. Results:The restdts from in vivo CTL assay showed that the CTL lysis activities were 37.3% ±7. 3%, 10. 8% ±2. 3%, 56.9% ±3.6% and 61.0% ±4. 2% via s. c. , i.m. , i.v. , and i.p. administration, respectively. Similarly, ICS showed that IFN-γ-producting cells in total CD8 ^+T lymphocytes were 0. 43% ± 0. 09%, 0. 85% + 0. 12%, 0. 76% + 0. 14% and 0. 15% ±0. 04%, respectively. Conclusion: Different routes of administration has an obvious influence on vaccine efficiency of peptide-pulsed DC. The i. p. immunization with DC elicites the strongest CTL lysis activity, i.v. immunization is next, and s. c. , in particular i.m. is the worst, suggesting that i.p. administration may be a safe and effective route for immunization with peptide-pulsed DC against, cancers in a mice model.