1. T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice.
- Author
-
Montes VN, Turner MS, Subramanian S, Ding Y, Hayden-Ledbetter M, Slater S, Goodspeed L, Wang S, Omer M, Den Hartigh LJ, Averill MM, O'Brien KD, Ledbetter J, and Chait A
- Subjects
- Adipose Tissue drug effects, Adipose Tissue immunology, Animals, CD40 Ligand antagonists & inhibitors, CD40 Ligand immunology, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes immunology, CTLA-4 Antigen antagonists & inhibitors, CTLA-4 Antigen immunology, Diet, High-Fat, Immunomodulation, Inflammation immunology, Inflammation pathology, Insulin Resistance immunology, Lymphocyte Activation drug effects, Macrophages drug effects, Macrophages immunology, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Obesity immunology, Weight Gain drug effects, Weight Gain immunology, Adipose Tissue pathology, CD8-Positive T-Lymphocytes pathology, Immunoglobulins administration & dosage, Macrophages pathology, Obesity pathology
- 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.
- Published
- 2013
- Full Text
- View/download PDF