Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells
Invariant NKT cells exacerbate type 1 diabetes induced by CD8 T cells
复制标题
DOI：
10.4049/jimmunol.175.4.2091
复制
发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Lehuen, AS
中科院分区：
文献类型：
--
作者：
Griseri, T;Beaudoin, L;Lehuen, AS
不变的NKT（iNKT）细胞参与了自身免疫性疾病的调节。在几种I型糖尿病模型中，增加iNKT细胞的数量可以预防疾病的发展。由于CD 8 T细胞在糖尿病的发病机制中起着至关重要的作用，我们研究了iNKT细胞对糖尿病致CD 8 T细胞的影响。在本研究中，I型糖尿病是通过将对流感病毒血凝素特异性的CD 8 T细胞转移到在其13个胰腺细胞中特异性表达血凝素Ag的受体小鼠中来诱导的。与以前的报道相反，高频率的iNKT细胞促进了严重的胰岛炎并加重了糖尿病。致糖尿病性CD 8 T细胞的分析显示，iNKT细胞增强其活化、扩增和分化成产生IFN-γ的效应细胞。iNKT细胞对致糖尿病性CD 8 T细胞影响的首次分析表明，iNKT细胞不仅不能调节糖尿病的发展，而且实际上会加剧糖尿病的发展。因此，iNKT细胞可以诱导依赖于正在研究的1型糖尿病模型的相反作用。在开发基于iNKT细胞操作的治疗方法时，应考虑iNKT细胞的这种促糖尿病能力。
Invariant NKT (iNKT) cells have been implicated in the regulation of autoimmune diseases. In several models of type I diabetes, increasing the number of iNKT cells prevents the development of disease. Because CD8 T cells play a crucial role in the pathogenesis of diabetes, we have investigated the influence of iNKT cells on diabetogenie CD8 T cells. In the present study, type I diabetes was induced by the transfer of CD8 T cells specific for the influenza virus hemagglutinin into recipient mice expressing the hemagglutinin Ag specifically in their 13 pancreatic cells. In contrast to previous reports, high frequency of iNKT cells promoted severe insulitis and exacerbated diabetes. Analysis of diabetogenic CD8 T cells showed that iNKT cells enhance their activation, their expansion, and their differentiation into effector cells producing IFN-gamma. This first analysis of the influence of iNKT cells on diabetogenic CD8 T cells reveals that iNKT cells not only fail to regulate but in fact exacerbate the development of diabetes. Thus, iNKT cells can induce opposing effects dependent on the model of type 1 diabetes that is being studied. This prodiabetogenic capacity of iNKT cells should be taken into consideration when developing therapeutic approaches based on iNKT cell manipulation.