迟发型超敏反应(Delayed-type hypersensitivity, DTH)是具有相应抗原[1]的效应T细胞作用后,以单个核细胞浸润和组织细胞损伤为特征的炎症反应。它通常发生在细菌和病毒感染、肿瘤疾病、移植排斥和接触性皮炎期间。小鼠接触性超敏反应是一种广泛用于研究T细胞介导的接触性过敏原免疫反应的模型。恶唑酮(OXA)是一种半抗原,应用于皮肤时可与皮肤蛋白结合形成完整抗原,刺激T淋巴细胞增殖为致敏淋巴细胞[2]。4 ~ 7天后再次使用奥沙利铂,局部可出现迟发性过敏反应。钥孔血蓝蛋白(KLH)是一种高免疫原性蛋白大分子,可使树突状细胞识别Th1细胞[3],是诱发迟发性超敏反应的理想抗原。KLH被系统性地引入小鼠体内。几周后再次局部注射,通过注射部位相对肿胀度评估迟发性超敏反应。Biocytogen建立OXA和KLH诱导的迟发性超敏反应(DTH)小鼠(Balb/c)模型,可用于免疫抑制剂疗效评价。
OXA-Induced DTH Mouse Model
KLH-Induced DTH Mouse Model
Efficacy Evaluation of Dexamethasone and Anti-TNFα in a OXA-induced DTH Mouse Model
Figure 1. Dexamethasone and Anti-TNFα alleviate OXA-induced DTH. Five days after oxazolone sensitization, mice were treated with dexamethasone or anti-TNFα before the challenge. Ear thickness was recorded before and 24 hours after the challenge. (A) Ear thickness, (B) Change of ear thickness. Values are expressed as mean ± SEM. One-way ANOVA with Bonferroni test, n=5, *** p<0.001, **p<0.01 .
Figure 2. H&E staining result. The inflamed ears were analyzed by H&E staining (A), and the ear epidermis was evaluated (B). Values are expressed as mean ± SEM. One-way ANOVA with Bonferroni test, n=5, *** p<0.001, **p<0.01 .
Efficacy Evaluation of Dexamethasone on KLH-induced DTH model
Figure 3. Dexamethasone alleviates KLH-induced DTH. On Day 0, mice were immunized by intraperitoneal injection of KLH/CFA/IFA emulsion. On Day 7, mice were challenged by intradermal injection of KLH into the ear. Additionally, mice were administered with dexamethasone subcutaneously and ear thinkness was then measured on Day 8, Day 9 and Day 10. (A) Body weight, (B) Ear thickness and (C) Epidermal score of ear. Values are expressed as mean ± SEM. * p<0.05
参考文献
[1] Honda T, Egawa G, Grabbe S, Kabashima K. Update of immune events in the murine contact hypersensitivity model: toward the understanding of allergic contact dermatitis. J Invest Dermatol. 2013. 133(2):303-15.
[2] Mchale J F , Harari O A , Marshall D , et al. Vascular endothelial cell expression of ICAM-1 and VCAM-1 at the onset of eliciting contact hypersensitivity in mice: evidence for a dominant role of TNF-alpha.[J]. American Association of Immunologists, 1999(3).
[3] Richerson HB, Dvorak HF, Leskowitz S. Cutaneous basophil hypersensitivity. I. A new look at the Jones-Mote reaction, general characteristics. J Exp Med. 1970. 132(3):546-57.