慢性粘膜免疫应答诱导的小鼠自身免疫综合征

Autoimmune syndrome induced by chronic mucosal immune response

空弯菌(CJ-S131)慢性感染小鼠具有SLE样自身免疫综合征。本文进一步用甲醛化空弯菌(CJ-S131菌苗)经口免疫BALB/c小鼠,每周两次,持续14周.模拟慢性感染时的慢性肠道粘膜免疫应答.发现免疫小鼠也具有SLE样自身免疫综合征,且较该菌慢性感染小鼠更显著。主要表现有:(1)全身免疫系统的淋巴组织显著增生;(2)B淋巴细胞多克隆激活;(3)多种自身抗体(包括抗ds-DNA.ss-DNA和组蛋白抗体)显著升高;(4)免疫复合物性肾小球肾炎;(5)多器官性(如肝、肠等组织)慢性炎症;(6)血管炎和血管周围炎。在体外自身免疫应答诱导实验中,免疫小鼠的脾细胞培养上清中,免疫球蛋白(总Ig)和抗DNA抗体显著高于非免疫小鼠。上述结果证实.空肠弯菌慢性感染所致的自身免疫综合征.和该菌抗原诱导的慢性肠道粘膜免疫应答有关。本实验为研究感染和自身免疫的关系提供了实用的动物模型。

To explore me chanisms of successful induction of autoimmunity by chronic Campylobacter jejuni (CJ-S131 ) infection [3, 4, 5, 6], a chronic mucosal immune response mooe(?) was established by oral immunization of BALB /C mice with formalized CJ-S131 bacteria.in a dosage of 4 xlO8 bacterial cells per mouse, twice a week for 14 weeks, which mimicked the released antigens persistently stimulating the mucosal immune system when mice were chronically infected by C. jejuni. It was also found that the immunized mice demonstrated (?)upus-like autoimmune syndro me, sim ilar, but more severe.to those seen in the mice chronically infected by C. jejuni. It was characterized by (1) significant lymphoproliferation of both mucosal and systemic immune systems; (2) polyclonal activation of B lymphocytes; (3) significantly elevated level of multiple autoanti bodies against ss- DNA, ds- DNA and histones; (4) immunocom plex glomerulonephritisi; (5) chronic inflammation of multiple organs or tissues including the intestine, liver and blood vessels. In the polyclonal activation testin vitro, the levels of total immunoglobulins and autoantibody against DNA in the supernatan ts of the splenic culture cells from the immunized mice were significantly higher than that from the controll mice. The results verified that chronic C. jejuni infection in the gut could induce abnormal. chronic mucosal immune response which led to perturbation of the systemic immune system, resulting autoimmunity or autoimmune syndrom.