NKT cell defects in NOD mice suggest therapeutic opportunities.
NKT cell defects in NOD mice suggest therapeutic opportunities.
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NOD 小鼠的 NKT 细胞缺陷提示了治疗机会。
作者：
A. Kukreja;Guilia Costi;J. Marker;Chen Hui Zhang;S. Sinha;Zhongsheng Sun;N. Maclaren
最近的研究报道，免疫调节NKT细胞在NOD小鼠中是有缺陷的，并且用选择性刺激NKT细胞的α-半乳糖神经酰胺治疗小鼠是抗糖尿病的。本研究的目的是记录NOD小鼠在糖尿病发作前各器官中NKT细胞变化的自然史，以便设计新的干预疗法。我们发现，NKT细胞特异性受体（NKT-TCR）Valpha 14 Jalpha 281的表达定量（实时）RT-PCR的NOD雄性和雌性小鼠的胸腺，脾脏和肝脏在1-3个月的生活相比，BALB/c和C57 BL/6小鼠低，虽然在2个月的雌性NOD肝脏中发生了短暂的高峰水平。女性胰腺表现出低水平的这些成绩单，尽管他们的积极和破坏性胰岛炎。相比之下，NOD男性在胰腺中表现出这种恒定TCR的高表达，其中他们的胰岛炎破坏性较小。在一组同源的非糖尿病易感NOD菌株中NKT-TCR表达的调查表明，这种NKT表型是相当可变的，但高于糖尿病易感NOD。NOD女性B6.NOD-H2（g7）供者骨髓移植后NKT-TCR表达增加。以已知的保护NOD小鼠免于糖尿病的方式给予BCG和CFA形式的阿曲库林都提高了NKT-TCR水平，抗炎PPAR-gamma激动剂罗格列酮也是如此。这些发现提供了令人兴奋的治疗途径，以探索在人类免疫介导的1型糖尿病，其中有类似的免疫调节病变的治疗。
Recent studies have reported that immunoregulatory NKT cells are defective in NOD mice and that treatment of mice with alpha-galactosylceramide that selectively stimulate NKT cells, is anti-diabetogenic. The objective of this study was to document the natural history of changes in NKT cells in various organs in NOD mice in the period up to the time of diabetes onset so that novel intervention therapies could be devised. We found that NKT cell-specific receptor (NKT-TCR) Valpha14Jalpha281 expressions by quantitative (RealTime) RT-PCR in thymus, spleen and liver of NOD male and female mice were low at 1-3 months of life compared to BALB/c and C57BL/6 mice, albeit a transient spike in levels occurred in female NOD livers at 2 months. Female pancreases showed low levels of these transcripts despite their active and destructive insulitis. In contrast, NOD males exhibited high expression of this invariant TCR in pancreas, where their insulitis was less destructive. A survey of NKT-TCR expressions in a battery of congenic, non-diabetes prone NOD strains indicated that this NKT phenotype was quite variable but higher than diabetes prone NOD. Bone marrow transplantation of NOD females from B6.NOD-H2(g7) donors raised their NKT-TCR expressions. Tuberculin administrations in the forms of BCG and CFA in a manner known to protect NOD mice from diabetes both raised NKT-TCR levels, as did the anti-inflammatory PPAR-gamma agonist rosiglitazone. These findings provide exciting therapeutic avenues to be explored in the treatment of human immune mediated type-1 diabetes where there are similar immunoregulatory lesions.
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影响因子：
4.4
作者：
B. Yankelevich;C. Knobloch;M. Nowicki;G. Dennert
通讯作者：
B. Yankelevich;C. Knobloch;M. Nowicki;G. Dennert
影响因子：
32.4
作者：
Salomon, B;Lenschow, DJ;Bluestone, JA
通讯作者：
Bluestone, JA
NOD 小鼠抗原呈递细胞和自身免疫性糖尿病的免疫遗传学。
DOI：
--
发表时间：
1992
期刊：
Regional immunology
影响因子：
--
作者：
Leiter,EH;Serreze,DV
通讯作者：
Serreze,DV
糖尿病疫苗：一个有待实现的未来。
DOI：
10.1089/15209150152607222
发表时间：
2001
期刊：
Diabetes technology & therapeutics.
影响因子：
--
作者：
Lin-Su,K;Kukreja,A;Maclaren,NK
通讯作者：
Maclaren,NK
影响因子：
15.9
作者：
Kukreja, A;Cost, G;Maclaren, N
通讯作者：
Maclaren, N