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目的 :应用B7- 1和B7- 2反义寡核苷酸 (ASB7- 1/ASB7- 2oligo)抑制CD80 (B7- 1)、CD86 (B7- 2 )在供体小鼠骨髓树突状细胞 (DC)上的表达 ,观察这类DC对同种异体小鼠心脏移植存活时间的影响并探讨其机理。方法 :小鼠B7- 1和B7- 2反义寡核苷酸在lipofectamine协助下分别转染供体鼠C5 7BL/10J(B10 )小鼠骨髓DC ,流式细胞仪检测其CD80 /CD86的表达 ,证实为CD80 low/CD86 low。将各组DC经尾静脉输注到受体小鼠C3H/HeJ(C3H)体内 ,1周后进行心脏移植术 ,观察存活时间 ;体外实验观察各组DC对同种异体T细胞的激活作用 ,包括混合淋巴细胞反应、细胞毒性效应、及IL - 2的产生。结果 :ASB7- 1和ASB7- 2分别显著抑制DC表达CD80 /CD86 ;转输这些CD80 low/CD86 lowDC可使小鼠心脏移植物存活时间显著延长 ,分别为 (18.6± 0 .89)d和 (2 3.6 7± 10 .73)d ,与转输成熟骨髓DC(IL - 4DC)组和生理盐水注射组(6 .2 2± 0 .97)d、(11.17± 1.72 )d比较 ,均有显著差异 (P <0 0 1) ;CD80 low或CD86 lowDC对异体T细胞激活作用较弱 ,表现为T细胞增殖能力、IL - 2产生及细胞毒杀伤均明显低。结论 :应用反义寡聚核苷酸转染供者DC ,降低其CD80或CD86的表达 ,可以抑制供者特异性的免疫应答 ,延长移植物存活时间。
OBJECTIVE: To investigate the inhibitory effect of B7-1 and B7-2 antisense oligonucleotides (ASB7-1 / ASB7-2oligo) on CD80 (B7-1) and CD86 (B7-2) on murine bone marrow dendritic cells DC) on the expression of allogeneic mouse heart transplantation to observe the survival time and explore its mechanism. Methods: The murine B7-1 and B7-2 antisense oligonucleotides were transfected into donor murine C5 7BL / 10J (B10) mouse bone marrow DCs respectively with the help of lipofectamine. The expression of CD80 / CD86 was detected by flow cytometry , Confirmed as CD80 low / CD86 low. Each group of DCs were transplanted into the recipient mice C3H / HeJ (C3H) via the tail vein. One week later, heart transplantation was performed and the survival time was observed. The activation of allogeneic T cells was observed in vitro, Including mixed lymphocyte reactions, cytotoxic effects, and IL-2 production. Results: The expression of CD80 / CD86 was significantly inhibited by ASB7-1 and ASB7-2, respectively. The transdifferentiation of these CD80low / CD86lowDC could prolong the survival of cardiac allografts significantly (18.6 ± 0.89) d and ( 2 3.6 7 ± 10 .73 d) was significantly higher than that in the mature bone marrow DC (IL - 4DC) group and the saline injection group (6.22 ± 0.97) d, (11.17 ± 1.72) d (P <0.01). The activation of allogeneic T cells by CD80 low or CD86 lowDC was weak, which showed that T cell proliferation, IL - 2 production and cytotoxicity were all significantly lower. CONCLUSION: Transfection of donor DCs with antisense oligonucleotides reduces the expression of CD80 or CD86, inhibits donor-specific immune responses and prolongs graft survival.