MYCOBACTERIA PRECIPITATE AUTOIMMUNE RHEUMATIC DISEASE IN NOD MICE VIA AN ADJUVANT-LIKE ACTIVITY
MYCOBACTERIA PRECIPITATE AUTOIMMUNE RHEUMATIC DISEASE IN NOD MICE VIA AN ADJUVANT-LIKE ACTIVITY
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DOI：
10.1111/j.1365-3083.1994.tb03419.x
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发表时间：
1994-06-01
影响因子：
3.7
通讯作者：
COOKE, A
中科院分区：
文献类型：
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作者：
BAXTER, AG;HEALEY, D;COOKE, A
NOD小鼠自发产生器官特异性自身免疫，被广泛用作糖尿病模型。NOD小鼠也表现出非器官特异性自身免疫性风湿病的一些特征，如胸腺细胞毒性和抗核自身抗体，并在衰老时发生溶血性贫血。8周龄NOD小鼠单剂量注射2.6x10(7)热杀卡介苗（BCG）可预防糖尿病，但会诱发类似系统性红斑狼疮（SLE）的综合征，治疗小鼠迅速出现溶血性贫血、高滴度抗dna和抗sm抗核自身抗体、肾脏血管周围淋巴细胞浸润和肾小球免疫复合物沉积。在这里，我们研究了卡介苗在NOD小鼠中诱发风湿性自身免疫性疾病的作用机制。注射后2周，bcg处理的NOD小鼠网状内皮细胞功能显著增强。到4周时，治疗小鼠的Mac-1（+）和ii类+，b220阴性脾细胞增加了3至4倍，体外抗原呈递能力增强了2至4倍。体内对SRBC的反应证实了卡介苗注射后4周的DTH增强，与佐剂样活性一致。
NOD mice spontaneously develop organ-specific autoimmunity and are widely used as a model for diabetes. NOD mice also exhibit some features of non-organ specific autoimmune rheumatic disease such as thymocytotoxic and anti-nuclear autoantibodies and they develop haemolytic anaemia in senescence. A single dose of 2.6x10(7) heat-killed Bacillus Calnette-Guerin (BCG) i.v. in 8-week-old NOD mice prevented diabetes but precipitated a syndrome similar to systemic lupus erythematosus (SLE), in which treated mice rapidly developed haemolytic anaemia, high titre anti-DNA and anti-Sm antinuclear autoantibodies, perivascular lymphocytic infiltration in the kidneys and glomerular immune complex deposition. Here, we examined the mechanism of action by which BCG precipitated rheumatic autoimmune disease in NOD mice. Two weeks after injection, reticuloendothelial cell function was dramatically increased in BCG-treated NOD mice. By 4 weeks, treated mice had a three- to four-fold increase in Mac-1(+) and class-II+, B220-negative splenocytes and in vitro antigen-presentation capacity was enhanced two- to four-fold. In vivo responses to SRBC confirmed enhancement of DTH 4 weeks after BCG injection, consistent with an adjuvant-like activity.