Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: implications for human studies
Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: implications for human studies
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DOI：
10.1046/j.1440-1711.2004.01238.x
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发表时间：
2004-06-01
影响因子：
4
通讯作者：
Godfrey, DI
中科院分区：
文献类型：
--
作者：
Berzins, SP;Kyparissoudis, K;Godfrey, DI
在易患糖尿病的NOD小鼠中，NKT细胞的系统性缺乏与1型糖尿病的发病之间存在已证实的关联。许多关于人类1型糖尿病患者NKT细胞区室内类似缺陷的报道表明，NKT细胞水平可能是易感性的有价值的预测因子，并可提供治疗干预的靶点。然而，最近的两项研究发现，1型糖尿病与人类血液NKT细胞水平之间没有关联，因此拒绝了糖尿病发作与NKT细胞缺乏之间的联系。这对基于NKT细胞的临床应用潜力产生了相当大的怀疑，并对NOD小鼠作为人类1型糖尿病模型的有效性提出了挑战。我们现在报告说，血液中的NKT细胞水平与其他器官中的NKT细胞水平相比代表性较差。引人注目的是，在NOD小鼠中发现了系统性NKT细胞缺陷，血液水平正常，甚至升高。这重新建立了NKT细胞缺乏和1型糖尿病之间的相关性，并提出了关于人体NKT细胞水平测定的重要问题。
In the diabetes-prone NOD mouse, there is a proven association between a systemic deficiency of NKT cells and the onset of type 1 diabetes. Numerous reports of similar defects within the NKT cell compartment of human type 1 diabetes patients suggested NKT cell levels might be a valuable predictor of susceptibility and could provide a target for therapeutic intervention. Two recent studies, however, found no association between type 1 diabetes and blood NKT cell levels in humans and consequently rejected a link between the onset of diabetes and NKT cell deficiency. This cast considerable doubts on the potential for NKT cell-based clinical applications and challenged the validity of the NOD mouse as a model of human type 1 diabetes. We now report that NKT cell levels in blood are a poor representation of those in other organs. Strikingly, systemic NKT cell deficiencies were identified in NOD mice with normal, or even raised, blood levels. This re-establishes the correlation between NKT cell deficiency and type 1 diabetes and raises important questions regarding the assaying of NKT cell levels in humans.