耐受性树突状细胞预防和治疗卵清蛋白过敏小鼠的的研究

Preventive and therapeutic effects of tolerogenic dendritic cells on ovalbulmin sensitized mice

目的比较腺病毒重组CTLA4Ig/α4β7诱导的耐受性树突状细胞对卵清蛋白(OVA)致敏小鼠的预防和治疗效果。方法 BALA/c小鼠32只,分为4组。基础致敏24 h后回输耐受性树突状细胞为预防组;肠道激发4 h后回输耐受性树突状细胞为治疗组;回输生理盐水为阴性对照组和OVA过敏小鼠为阳性对照组。观察各组小鼠过敏症状缓解情况;HE染色观察空肠形态;甲苯胺兰染色观察小肠固有层肥大细胞聚集及脱颗粒现象;ELISA测定各组血清中OVA特异性IgE水平。结果与阳性对照组相比,治疗组小鼠OVA特异性IgE水平显著降低(0.25±0.05 vs 0.17±0.03)(P<0.05);体重增长明显(3.16 g±0.75 g vs 5.04 g±0.49 g)(P<0.05);腹泻症状减轻;HE染色可见治疗组小肠绒毛中上皮细胞局灶性坏死、脱落,固有层炎症细胞浸润现象明显改善;肥大细胞聚集和脱颗粒现象改善。而预防组较阳性对照组过敏症状、小肠形态学及OVA特异性IgE水平差异均无统计学意义。结论 Ad CTLA4Ig/Adα4β7修饰的致耐受性树突状细胞对卵清蛋白过敏小鼠具有治疗作用而无预防作用。

Objective To investigate the preventative and therapeutic effects of Ad CTLA4Ig/Adα4β7-dendritic cells （DCs） in the ovalbulmin （OVA） sensitized BALB/c mice. Method 32 female BALB/c mice aged 4 - 6 weeks fed on the ovalbulmin-free diet were randomly divided into 4 groups ： （ 1 ） preventive group ： administered tolerogenic DCs after being basic sensitized; （2） treatment group： the OVA sensitized mice were injected tolerogentic Ad CTLA4Ig/Adα4β7- DCs after being challenged with OVA; （3） negative control group： mice were sensitized and challenged with normal saline; （4） positive control group： mice were sensitized and challenged with OVA. The symptoms were observed and recorded. The jejunal samples were observed histologically after HE staining. The levels of the OVA-specific IgE in serum were measured by ELISA. Result Compared with the positive group, the level of serum OVA-specific IgE in the treatment group was reduced significantly （0.25 ± 0.05 vs 0.17 ± 0.03 ） （ P 〈 0.05 ） ; diarrhea symptom almost diappeared. And the inflammatory reactions, the accumulation of the lymphocytes and plasmacytes in lamina propria （ LP）, the focal necrosis and shedding of the epithelial cells in intestinal villi, accumulated and degranulated mast cells in LP, were remarkedly relieved in the treatment group compared with positive group. All these indexes showed no significant difference between positive group and preventive group. Conclusion This study demonstrated that caudal vein injection with tolerogentic Ad TLA4Ig/ Aα4β7-DC seems to be of potential value in the treatment of food allergy instead of preventative effect.