Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice
Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice
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DOI：
10.1038/nm1296-1348
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发表时间：
1996-12-01
期刊：
影响因子：
82.9
通讯作者：
Kaufman, DL
中科院分区：
文献类型：
--
作者：
Tian, JD;ClareSalzler, M;Kaufman, DL
在非肥胖糖尿病（NOD）小鼠中，β细胞反应性t辅助型1 （Th1）反应自发发展并逐渐扩散，产生一系列反应，最终破坏β细胞。自身反应性t细胞库的多样性造成了治疗方法发展的主要障碍。我们表明，即使存在既定的Th1反应，也有可能诱导自身抗原特异性抗炎Th2反应。t细胞对β细胞自身抗原谷氨酸脱羧酶（GAD65）反应的免疫偏差，诱导了一种活性形式的自我耐受性，这与糖尿病前期小鼠疾病进展的抑制和糖尿病NOD小鼠同基因胰岛移植物的延长存活有关。因此，调节自身抗原特异性Th1/Th2平衡可能提供了一种微创手段，下调已建立的致病性自身免疫反应。
In nonobese diabetic (NOD) mice, beta-cell reactive T-helper type 1 (Th1) responses develop spontaneously and gradually spread, creating a cascade of responses that ultimately destroys the beta-cells. The diversity of the autoreactive T-cell repertoire creates a major obstacle to the development of therapeutics. We show that even in the presence of established Th1 responses, it is possible to induce autoantigen-specific anti-inflammatory Th2 responses. Immune deviation of T-cell responses to the beta-cell autoantigen glutamate decarboxylase (GAD65), induced an active form of self-tolerance that was associated with an inhibition of disease progression in prediabetic mice and prolonged survival of syngeneic islet grafts in diabetic NOD mice. Thus, modulation of autoantigen-specific Th1/Th2 balances may provide a minimally invasive means of downregulating established pathogenic autoimmune responses.