CTLA4-Ig对变应性接触性皮炎小鼠模型的治疗作用  

Treatment of Murine Allergic Contact Dermatitis with CTLA4-Ig

作　　者：周倩[1] 寇庚[1] 钱卫珠[1] 王皓[1] 刘彦君[1] 王晓芸[1] 宋水川[1] 金军[1] 李晓冬[1] 吴孟超[2] 郭亚军[1] 陈列平 

机构地区：[1]第二军医大学国际合作肿瘤研究所,上海200433 [2]第二军医大学东方肝胆外科研究所 [3]美国莫尔医学院免疫学系

出　　处：《中华皮肤科杂志》2002年第4期256-259,共4页Chinese Journal of Dermatology

基　　金：国家自然科学基金资助(39928012)

摘　　要：目的探讨B7/CD28共刺激通路阻断剂CTLA4-Ig对变应性接触性皮炎的作用。方法建立小鼠二硝基氟苯(DNFB)变应性接触性皮炎模型,以不同剂量的CTLA4-Ig进行静脉注射,通过检测小鼠耳廓肿胀度观察其对DNFB和FITC刺激的反应,并观察CTLA4-Ig的长期疗效,同时对治疗后的小鼠脾细胞进行体外淋巴细胞增殖实验。结果CTLA4-Ig有明显的治疗作用,DNFB变应性接触性皮炎小鼠经治疗耳廓肿胀抑制率最高达69.7%,而且治疗的小鼠在激发后的14d用DNFB再刺激能产生无应答反应,但对FITC的再刺激表现为耳廓肿胀明显,过继转移CTLA4-Ig治疗小鼠的淋巴细胞能诱导受体鼠对DNFB的刺激产生特异性免疫耐受。结论应用B7/CD28共刺激通路阻断剂CTLA4-Ig融合蛋白能有效地抑制接触性超敏反应,为临床治疗Ⅳ型变态反应性皮肤病如湿疹等提供一种新的可能的治疗策略。Objective To study the effects of CTLA4-Ig on mu rine allergic contact dermatitis.Methods Mice were exposed to DNFB to induce allergic contact dermatitis and were i njected with CTLA4-Ig.Ear swelling was measured 24h after antigen challenge.Splenocytes from treated mice were assayed for their ability to prolif erate in response to DNFB or FITC stimulation in vitro.Results Profound inhibition of contact hypersensitivity response(CHS )was shown by 69.7%in mice treated with CTLA4-Ig compared with mice treate d with PBS control.CT-LA4-Ig-treated mice displayed DNFB-specific tolerance,but exhibited a vigorous immune response to FITC when re-sensitizing 14days after the fir st challenge.Adoptive transfer of l ymphocytes from CTLA4-Ig-treated mice could induce inhibition of CHS in recipien t mice.Conclusions CTLA4-Ig can inhibit CHS by blocking B7/CD28co-stimulatory pathway,which provides a new way to suppress typeⅣallergic reaction.[

关 键 词：CTLA4-IG 变应性接触性皮炎 接触性超敏反应 药理学 

分 类 号：R758.22[医药卫生—皮肤病学与性病学] R965[医药卫生—临床医学]