Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping
Adoptive transfer of regulatory NKT lymphocytes ameliorates non-alcoholic steatohepatitis and glucose intolerance in ob/ob mice and is associated with intrahepatic CD8 trapping
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DOI：
10.1002/path.1950
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发表时间：
2006-05-01
影响因子：
7.3
通讯作者：
Ilan, Y
中科院分区：
文献类型：
--
作者：
Elinav, E;Pappo, O;Ilan, Y
本研究旨在探讨过继转移调节性自然杀伤T（NKT）淋巴细胞对瘦素缺陷型ob/ob小鼠代谢紊乱的影响。对瘦素缺陷型ob/ob小鼠移植1 × 106 ob/ob或野生型来源的NKT淋巴细胞，或移植ob/ob或野生型来源的脾细胞。通过磁共振成像（信号强度指数）和组织学，使用脂肪性肝炎分级量表测量对肝脏脂肪含量的影响。通过口服葡萄糖耐量试验（GTT）测量葡萄糖耐受不良的程度。野生型或ob/ob衍生的调节性NKT细胞的过继转移导致肝脏脂肪含量减少12%。观察到从大脂肪变性到小脂肪变性的显著组织学变化。在野生型或ob/ob衍生的NKT受体中观察到GTT的显著改善。代谢效应与外周和肝内CD 4/CD 8淋巴细胞比率显著降低相关。在所有应答者中观察到肝内CD 8捕获。血清白细胞介素10水平显著降低。总之，过继转移相对少量的调节性NKT淋巴细胞到ob/ob小鼠中导致肝脏脂肪含量显著降低，从大脂肪变性转变为微小脂肪变性，以及葡萄糖耐受不良的显著改善。这些作用与外周和肝内CD 4/CD 8比值降低和白细胞介素10水平降低相关。这些结果进一步支持了调节性NKT淋巴细胞在瘦素缺陷小鼠模型中非酒精性脂肪性肝炎发病机制中的作用。版权所有（c）2006大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
The aim of this study was to determine the effect of adoptive transfer of regulatory natural killer T (NKT) lymphocytes on the metabolic disorder in leptin-deficient ob/ob mice, which feature depletion and defective function of NKT and CD4 lymphocytes. Leptin-deficient ob/ob mice were subjected to transplantation of 1 x 10(6) of either ob/ob or wild-type-derived NKT lymphocytes, or to transplantation of either ob/ob or wild-type-derived splenocytes. The effect on hepatic fat content was measured by magnetic resonance imaging (signal intensity index) and histology, using the steatohepatitis grading scale. The degree of glucose intolerance was measured by an oral glucose tolerance test (GTT). Adoptive transfer of wild-type or ob/ob-derived regulatory NKT cells led to a 12% decrease in hepatic fat content. A significant histological shift from macrosteatosis to microsteatosis was observed. Marked improvement in the GTT was noted in wild-type or ob/ob-derived NKT recipients. Metabolic effects were associated with a significant decrease in peripheral and intrahepatic CD4/CD8 lymphocyte ratios. Intrahepatic CD8 trapping was observed in all responders. Serum interleukin 10 levels decreased significantly. In conclusion, adoptive transfer of a relatively small number of regulatory NKT lymphocytes into ob/ob mice results in a significant reduction in hepatic fat content, a shift from macro to microsteatosis, and significant improvement in glucose intolerance. These effects were associated with decreased peripheral and intrahepatic CD4/CD8 ratios and decreased interleukin 10 levels. The results further support a role for regulatory NKT lymphocytes in the pathogenesis of non-alcoholic steatohepatitis in the leptin-deficient murine model. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.