T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese mice

• Published in: PloS one Vol. 8; no. 7; p. e67709
• Main Authors: 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, Chait, Alan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.07.2013; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - immunology; Adipose Tissue - pathology; Analysis; Animal models; Animal tissues; Animals; Bioaccumulation; Biology; Body fat; Body weight gain; CD40 Ligand - antagonists & inhibitors; CD40 Ligand - immunology; CD40L protein; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell activation; CTLA-4 Antigen - antagonists & inhibitors; CTLA-4 Antigen - immunology; CTLA-4 protein; Diet, High-Fat; Genetic aspects; Immunoglobulin G; Immunoglobulins - administration & dosage; Immunomodulation; Inflammation; Inflammation - immunology; Inflammation - pathology; Inhibitors; Insulin; Insulin resistance; Insulin Resistance - immunology; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - pathology; Male; Medicine; Mice; Mice, Inbred C57BL; Mice, Obese; Nutrition; Obesity; Obesity - immunology; Obesity - pathology; Recruitment; Rodents; T cell receptors; T cells; Weight Gain - drug effects; Weight Gain - immunology; Weight reduction
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067709

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.