Genetic dissection of Vα14Jα18 natural T cell number and function in autoimmune-prone mice
Genetic dissection of Vα14Jα18 natural T cell number and function in autoimmune-prone mice
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DOI：
10.4049/jimmunol.170.11.5429
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发表时间：
2003-06-01
影响因子：
4.4
通讯作者：
Joyce, S
中科院分区：
文献类型：
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作者：
Matsuki, N;Stanic, AK;Joyce, S
非肥胖型糖尿病（NOD）小鼠是I型糖尿病（TID）的模型，其不变的Valpha14Jalpha18 TCR α链阳性天然T （iNKT）细胞数量减少，这些细胞不释放IL-4，以响应其Ag受体在体内的激活。iNKT细胞数量和功能的缺陷与免疫失调和TID的病因有关。因此，我们推断控制iNKT细胞数量和功能的遗传决定因素可能位于Idd（胰岛素依赖性糖尿病易感基因座）区域，该区域已知含有TID抗性或易感基因。一项对Idd基因小鼠iNKT细胞数量和功能的系统分析显示，iNKT细胞数量和它们在体内急性Ag激活时不能快速分泌IL-4的能力都不是Idd基因小鼠预防糖尿病的机制。此外，iNKT细胞数量和功能的调控似乎受到几个基因的控制。其中最值得注意的是小鼠基因组的Idd4、Idd5、Idd9.1和Idd13区域。总之，这些发现为NOD小鼠iNKT细胞缺乏的遗传机制提供了线索。
Nonobese diabetic (NOD) mice, a model for type I diabetes (TID), have reduced numbers of invariant Valpha14Jalpha18 TCR alpha-chain-positive natural T (iNKT) cells that do not release IL-4 in response to in vivo activation through their Ag receptor. The deficit in iNKT cell number and function is implicated in immune dysregulation and the etiology of TID. Therefore, we reasoned that the genetic determinant(s) that controls iNKT cell number and function might lie within Idd (insulin-dependent diabetes susceptibility locus) regions, which are known to contain TID resistance or susceptibility genes. A systematic analysis of iNKT cell number and function in Idd congenic mice revealed that neither iNKT cell number nor their inability to rapidly secrete IL-4 in response to acute in vivo activation by Ag underlies the mechanism of protection from diabetes in Idd congenic mice. Moreover, the regulation of iNKT cell number and function appears to be under the control of several genes. The most notable of these map to the Idd4, Idd5, Idd9.1, and Idd13 regions of the mouse genome. Together these findings provide a clue to the genetic mechanism(s) underlying iNKT cell deficiency in NOD mice.