经鼻黏膜诱导免疫耐受治疗实验性自身免疫性葡萄膜炎

目的探讨经鼻腔滴注牛视网膜S抗原诱导免疫耐受对Lewis大鼠自身免疫性葡萄膜视网膜炎(EAU)的影响。方法利用盐析和离子交换层析方法纯化牛视网膜S抗原,然后用其诱导Lewis大鼠鼻黏膜耐受,再用视网膜S抗原诱发EAU,观察EAU的发病情况、眼部临床表现、组织学改变、皮肤迟发型超敏反应、由视网膜S抗原和刀豆蛋白A刺激的淋巴细胞增殖反应,同时观察环磷酰胺对免疫耐受的影响。结果用牛视网膜S抗原鼻腔滴注诱导免疫耐受后再诱导EAU,耐受组8只大鼠仅有2只发病(25%),对照组6只(100%)全部发病,耐受组大鼠发病比例明显低于对照组(P=0·0097)。耐受组大鼠的发病开始时间平均为16·5d,对照组为10·3d,两者之间差异有统计学意义(F=26·32,P=0·000;q=9·723,P<0·01);耐受组大鼠EAU病变的临床评分为0·89,对照组为3·94,差异有统计学意义(F=12·48,P=0·000;q=7·904,P<0·01);耐受组大鼠的组织学分级为1·21,对照组为4·12,差异有统计学意义(F=11·80,P=0·000;q=7·510,P<0·01)。耐受组大鼠的EAU表现为虹膜血管轻度扩张,前房和玻璃体内少量炎性渗出,视网膜轻度肿胀,视网膜感光细胞损害均较轻。耐受组大鼠的皮肤迟发型超敏反应和由视网膜S抗原刺激的淋巴细胞增殖反应也明显轻于对照组;腹腔注射环磷酰胺可轻度增强S抗原诱导的免疫耐受作用,仅用环磷酰胺对EAU的炎性反应无明显影响。结论视网膜S抗原诱导的黏膜耐受可有效地预防由视网膜S抗原诱发的EAU。

The suppression of the experimental autoimmune uveoretinitis with retinal S antigens by intranasal tolerance induction

Objective The aim was to investigate the suppression of rat experimental autoimmune uveoretinitis(EAU) by induced immune tolerance via intranasal administration of retinal S antigens. Methods The bovine S antigen was purified from bovine retina by salt precipitation and ionic exchange chromatography, the female Lewis rats were used to induce immune tolerance by intranasal administration with purified bovine retinal S antigens and then the rats were used to produce the EAU model by retinal S antigens challenge. The rate of EAU occurrence, the clinical and histological scores, the skin delayed-type hypersensitivity and lymphocyte proliferation stimulated by retinal S antigen and concanavalin A were recorded. The adjunct effect of cyclophosphamide on tolerance induction was observed. Results After intranasal administration of retinal S antigens, EAU was induced in two of eight(25%) rats in tolerant group, sis of six(100%) rats in control group , the difference of EAU induction rate was significant in tolerant group compared with control (P=0.0097). The average onset time in tolerant group were 16.5 days, the control group was 10.3 days, the difference was significant (F=26.32,P=0.000; q=9.723, P< 0.01). The average clinical scores of EAU in tolerant group were 0.89, the control group was 3.94, the difference was significant(F=12.48,P=0.000; q=7.904,P<0.01). The average histological scores of EAU in tolerant group were 1.21, the control group was 4.12, the difference was significant(F=11.80, P= 0.000; q=7.510,P<0.01). The histological features in tolerant group were iris blood vessels slightly dilation, few exudates in anterior chamber and vitreous cavity; there were slighter retina swallow and the photoreceptors damages in the tolerant group. The skin delayed-type hypersensitivity and the proliferative responses of lymphocytes stimulated by S antigen and concanavalin A in tolerant group were slighter than that in the control group. Intraperitoneal injection of cyclophosphamide enhanced the effect of immune tolerance slightly. Only intraperitoneal injection of cyclophosphamide did not diminish the severity of the rat EAU. Conclusion The intranasal induced tolerance by retinal S antigens can suppress effectively the prevalence of rat experimental autoimmune uveoretinitis induced by retinal S antigens.