Regulatory Natural Killer T Cells Protect against Spontaneous and Recurrent Type 1 Diabetes
Regulatory Natural Killer T Cells Protect against Spontaneous and Recurrent Type 1 Diabetes
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调节性自然杀伤 T 细胞可预防自发性和复发性 1 型糖尿病
DOI：
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发表时间：
2002
影响因子：
5.2
通讯作者：
T. Delovitch
中科院分区：
文献类型：
--
作者：
S. Sharif;G. Arreaza;P. Zucker;T. Delovitch
摘要：自身免疫性疾病，特别是1型糖尿病（T1 D），可能是由免疫系统的失调引起的，这导致调节性T辅助2（Th 2）细胞的低反应性和自身免疫性Th 1细胞的促进。自然杀伤T（NKT）细胞是T细胞的一个小亚群，由于IL-4和IFN-γ分泌的快速爆发，在免疫调节中起着关键作用。这些细胞在有T1 D风险的个体以及非肥胖糖尿病（NOD）小鼠中功能和数量上都有缺陷。可以想象，通过纠正这一缺陷，可以实现对T1 D的保护。α-半乳糖神经酰胺（α-GalCer）以CD 1依赖性方式特异性结合NKT细胞，刺激这些细胞增殖并产生各种细胞因子，包括IFN-γ、IL-4和IL-10。在这篇综述中，我们提供的证据表明，多剂量α-GalCer治疗方案（已知可促进优势Th 2环境）可预防自发性和环磷酰胺（CY）加速的T1 D发作。这种保护作用与受保护雌性NOD小鼠脾脏和胰腺中IL-4和IL-10的升高有关。同时，两种组织中的IFN-γ水平均降低。更重要的是，γ-GalCer在CY加速T1 D中的保护作用被IL-10活性的体内阻断所消除。我们还表明，α-GalCer治疗显著延长了受体糖尿病NOD小鼠的同基因胰岛移植物存活率。这些发现提高了α-GalCer治疗可用于治疗以预防人类T1 D的发作和复发的可能性。
Abstract: Autoimmune diseases, especially type 1 diabetes (T1D), may be caused by dysregulation of the immune system, which leads to hyporesponsiveness of regulatory T helper 2 (Th2) cells and promotion of autoimmune Th1 cells. Natural killer T (NKT) cells, which comprise a minor subpopulation of T cells, play a critical role in immunoregulation as a result of a rapid burst of IL‐4 and IFN‐γ secretion. These cells are functionally and numerically deficient in individuals at risk of T1D, as well as in nonobese diabetic (NOD) mice. It is conceivable that protection from T1D may be achieved by correction of this deficiency. Alpha‐galactosylceramide (α‐GalCer) specifically binds to NKT cells in a CD1‐dependent manner and stimulates these cells to proliferate and to produce various cytokines, including IFN‐γ, IL‐4, and IL‐10. In this review, we present evidence that a multiple‐dose α‐GalCer treatment regimen, which is known to promote a dominant Th2 environment, can prevent the onset of spontaneous and cyclophosphamide (CY)‐accelerated T1D. This protection is associated with elevated IL‐4 and IL‐10 in the spleen and pancreas of protected female NOD mice. Concomitantly, IFN‐γ levels are reduced in both tissues. More importantly, the protective effect of γ‐GalCer in CY‐accelerated T1D is abrogated by the in vivo blockade of IL‐10 activity. We also show that α‐GalCer treatment significantly prolongs syngeneic islet graft survival in recipient diabetic NOD mice. These findings raise the possibility that α‐GalCer treatment may be used therapeutically to prevent the onset and recurrence of human T1D.
DOI：
10.1073/pnas.93.20.11025
发表时间：
1996-10
影响因子：
11.1
作者：
M. Taniguchi;H. Koseki;T. Tokuhisa;K. Masuda;H. Sato;E. Kondo;T. Kawano;J. Cui;A. Perkes;S. Koyasu;Y. Makino
通讯作者：
M. Taniguchi;H. Koseki;T. Tokuhisa;K. Masuda;H. Sato;E. Kondo;T. Kawano;J. Cui;A. Perkes;S. Koyasu;Y. Makino
影响因子：
32.4
作者：
Salomon, B;Lenschow, DJ;Bluestone, JA
通讯作者：
Bluestone, JA
来自同卵双胞胎的调节性 Valpha 24Jalpha Q T 细胞的基因表达存在多重差异，与 I 型糖尿病不一致。
DOI：
10.1073/pnas.120161297
发表时间：
2000
影响因子：
11.1
作者：
Wilson,SB;Kent,SC;Horton,HF;Hill,AA;Bollyky,PL;Hafler,DA;Strominger,JL;Byrne,MC
通讯作者：
Byrne,MC