Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes
Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes
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DOI：
10.4049/jimmunol.174.3.1196
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Serreze, DV
中科院分区：
文献类型：
--
作者：
Chen, YG;Choisy-Rossi, CM;Serreze, DV
通过α-半乳糖神经酰胺（α-GalCer）的NKT细胞活化抑制NOD小鼠中的自身免疫性糖尿病，部分地通过诱导具有疾病保护作用的成熟树突状细胞（DC）募集到胰腺淋巴结（PLN）。然而，活化的NKT细胞如何促进DC成熟，以及这对致糖尿病T细胞的下游影响尚不清楚。发现活化的NKT细胞产生诱导DC成熟的可溶性因子。最初，在α-GalCer处理的NOD小鼠的PLN中存在成熟DC的优先积累，随后是T细胞的显著增加。致糖尿病性CD 8 T细胞群（AI 4）的连续转移在PBS治疗的NOD接受者中诱导了高发病率（75%），但在用α-GalCer预处理的接受者中没有诱导（8%）。值得注意的是，在α-GalCer的PLN中比PBS处理的受体中积累更多的AI 4 T细胞，而在来自各组的肠系膜淋巴结中没有发现差异。与肠系膜淋巴结相比，进入PLN的AI 4 T细胞经历了更高水平的凋亡，存活者变得功能性无能。NKT细胞的活化促进了这一过程。因此，活化的NKT细胞通过产生可溶性因子在NOD小鼠中引发糖尿病保护，所述可溶性因子诱导DC在PLN中成熟和积累，在PLN中它们随后募集并耐受致病性T细胞。
NKT cell activation by a-galactosylceramide (a-GalCer) inhibits autoimmune diabetes in NOD mice, in part by inducing recruitment to pancreatic lymph nodes (PLNs) of mature dendritic cells (DCs) with disease-protective effects. However, how activated NKT cells promote DC maturation, and what downstream effect this has on diabetogenic T cells was unknown. Activated NKT cells were found to produce a soluble factor(s) inducing DC maturation. Initially, there was a preferential accumulation of mature DCs in the PLNs of a-GalCer-treated NOD mice, followed by a substantial increase in T cells. Adoptive transfer of a diabetogenic CD8 T cell population (AI4) induced a high rate of disease (75%) in PBS-treated NOD recipients, but not in those pretreated with alpha-GalCer (8%). Significantly, more AI4 T cells accumulated in PLNs of alpha-GalCer than PBS-treated recipients, while no differences were found in mesenteric lymph nodes from each group. Compared with those in mesenteric lymph nodes, AI4 T cells entering PLNs underwent greater levels of apoptosis, and the survivors became functionally anergic. NKT cell activation enhanced this process. Hence, activated NKT cells elicit diabetes protection in NOD mice by producing a soluble factor(s) that induced DC maturation and accumulation in PLNs, where they subsequently recruit and tolerize pathogenic T cells.