Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
PLoS One. 2013 Jul 2;8(7):e67709. doi: 10.1371/journal.pone.0067709. Print 2013.
Adipose tissue inflammation and specifically, pro-inflammatory macrophages are believed to contribute to insulin resistance (IR) in obesity in humans and animal models. Recent studies have invoked T cells in the recruitment of pro-inflammatory macrophages and the development of IR. To test the role of the T cell response in adipose tissue of mice fed an obesogenic diet, we used two agents (CTLA-4 Ig and anti-CD40L antibody) that block co-stimulation, which is essential for full T cell activation. C57BL/6 mice were fed an obesogenic diet for 16 weeks, and concomitantly either treated with CTLA-4 Ig, anti-CD40L antibody or an IgG control (300 µg/week). The treatments altered the immune cell composition of adipose tissue in obese mice. Treated mice demonstrated a marked reduction in pro-inflammatory adipose tissue macrophages and activated CD8+ T cells. Mice treated with anti-CD40L exhibited reduced weight gain, which was accompanied by a trend toward improved IR. CTLA-4 Ig treatment, however, was not associated with improved IR. These data suggest that the presence of pro-inflammatory T cells and macrophages can be altered with co-stimulatory inhibitors, but may not be a significant contributor to the whole body IR phenotype.
脂肪组织炎症，特别是促炎巨噬细胞，被认为是导致人类和动物肥胖模型胰岛素抵抗（IR）的原因。最近的研究表明，T 细胞在招募促炎巨噬细胞和 IR 发展中起作用。为了测试 T 细胞反应在喂食致肥胖饮食的小鼠脂肪组织中的作用，我们使用了两种阻断共刺激的试剂（CTLA-4 Ig 和抗 CD40L 抗体），这对于 T 细胞的完全激活是必需的。C57BL/6 小鼠喂食致肥胖饮食 16 周，同时用 CTLA-4 Ig、抗 CD40L 抗体或 IgG 对照（300 µg/周）处理。这些治疗改变了肥胖小鼠脂肪组织中的免疫细胞组成。治疗小鼠表现出促炎脂肪组织巨噬细胞和活化的 CD8+T 细胞明显减少。用抗 CD40L 治疗的小鼠体重增加减少，IR 趋势改善。然而，CTLA-4 Ig 治疗与改善 IR 无关。这些数据表明，促炎 T 细胞和巨噬细胞的存在可以用共刺激抑制剂改变，但可能不是全身 IR 表型的重要贡献者。
