T Cell Activation Inhibitors Reduce CD8+ T Cell and Pro-Inflammatory Macrophage Accumulation in Adipose Tissue of Obese Mice |
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Authors: | Vince N Montes Michael S Turner Savitha Subramanian Yilei Ding Martha Hayden-Ledbetter Sonya Slater Leela Goodspeed Shari Wang Mohamed Omer Laura J Den Hartigh Michelle M Averill Kevin D O’Brien Jeffrey Ledbetter Alan Chait |
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Institution: | 1. Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, United States of America.; 2. Benaroya Research Institute, Seattle, Washington, United States of America.; 3. Division of Rheumatology, University of Washington, Seattle, Washington, United States of America.; 4. Division of Cardiology, University of Washington, Seattle, Washington, United States of America.; University of Padova, Italy, |
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Abstract: | 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. |
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