Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells
Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells
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DOI：
10.1111/j.1365-2567.2008.02958.x
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发表时间：
2009-08-01
期刊：
影响因子：
6.4
通讯作者：
Mitre, Edward
中科院分区：
文献类型：
--
作者：
Hubner, Marc P.;Stocker, J. Thomas;Mitre, Edward
我们试图确定是否Litomosoides sigmodontis，一种啮齿动物的丝虫感染，保护非肥胖糖尿病（NOD）小鼠免受1型糖尿病的影响。将6周龄的NOD小鼠假感染或感染L3幼虫、成年雄性蠕虫或成年雌性蠕虫。然而，82%未感染的NOD小鼠在25周龄时发生糖尿病，没有L。感染乙状窦炎的小鼠出现疾病。尽管所有的小鼠都有组织学上持续的胰岛细胞炎症的证据，L。感染sigmodontis的小鼠比对照小鼠具有更多的总胰岛和未浸润的胰岛。对糖尿病的保护作用与辅助性T细胞2型（Th2）转移有关，因为在L.感染sigmodontis的小鼠比未感染的小鼠。胰岛素特异性免疫球蛋白G1的循环水平增加表明，这种Th2转变是对糖尿病中的一种主要自身抗原的反应。多色流式细胞术研究表明，L。感染sigmodontis的NOD小鼠与脾脏CD4（+）CD25（+）FoxP3（+）调节性T细胞数量显著增加相关。有趣的是，将粗制蠕虫抗原注射到NOD小鼠中也导致了对1型糖尿病的保护，尽管程度低于用活的L. S形齿蠕虫总之，这些研究表明，蠕虫可以预防NOD小鼠1型糖尿病的发生。这种保护作用与Th2移位有关，如细胞因子和抗体产生所证明的，并且与CD4（+）CD25（+）FoxP3（+）调节性T细胞的增加有关。
P>We sought to determine whether Litomosoides sigmodontis, a filarial infection of rodents, protects against type 1 diabetes in non-obese diabetic (NOD) mice. Six-week-old NOD mice were sham-infected or infected with either L3 larvae, adult male worms, or adult female worms. Whereas 82% of uninfected NOD mice developed diabetes by 25 weeks of age, no L. sigmodontis-infected mice developed disease. Although all mice had evidence of ongoing islet cell inflammation by histology, L. sigmodontis-infected mice had greater numbers of total islets and non-infiltrated islets than control mice. Protection against diabetes was associated with a T helper type 2 (Th2) shift, as interleukin-4 (IL-4) and IL-5 release from alpha-CD3/alpha-CD28-stimulated splenocytes was greater in L. sigmodontis-infected mice than in uninfected mice. Increased circulating levels of insulin-specific immunoglobulin G1, showed that this Th2 shift occurs in response to one of the main autoantigens in diabetes. Multicolour flow cytometry studies demonstrated that protection against diabetes in L. sigmodontis-infected NOD mice was associated with significantly increased numbers of splenic CD4(+) CD25(+) FoxP3(+) regulatory T cells. Interestingly, injection of crude worm antigen into NOD mice also resulted in protection against type 1 diabetes, though to a lesser degree than infection with live L. sigmodontis worms. In conclusion, these studies demonstrate that filarial worms can protect against the onset of type 1 diabetes in NOD mice. This protection is associated with a Th2 shift, as demonstrated by cytokine and antibody production, and with an increase in CD4(+) CD25(+) FoxP3(+) regulatory T cells.