1. T Cell Activation Inhibitors Reduce CD8+ T Cell and Pro-Inflammatory Macrophage Accumulation in Adipose Tissue of Obese Mice.
- Author
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Montes, Vince N., Turner, Michael S., Subramanian, Savitha, Ding, Yilei, Hayden-Ledbetter, Martha, Slater, Sonya, Goodspeed, Leela, Wang, Shari, Omer, Mohamed, Den Hartigh, Laura J., Averill, Michelle M., O’Brien, Kevin D., Ledbetter, Jeffrey, and Chait, Alan
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OBESITY , *T cells , *BIOACCUMULATION , *ADIPOSE tissues , *INSULIN resistance , *IMMUNOLOGY , *ATHEROSCLEROSIS , *LABORATORY mice - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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