title: T cell activation inhibitors reduce CD8+ T cell and pro-inflammatory macrophage accumulation in adipose tissue of obese 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.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA.
authors.forename: Vince N
authors.initials: VN
authors.lastname: Montes
authors.forename: Michael S
authors.initials: MS
authors.lastname: Turner
authors.forename: Savitha
authors.initials: S
authors.lastname: Subramanian
authors.forename: Yilei
authors.initials: Y
authors.lastname: Ding
authors.forename: Martha
authors.initials: M
authors.lastname: Hayden-Ledbetter
authors.forename: Sonya
authors.initials: S
authors.lastname: Slater
authors.forename: Leela
authors.initials: L
authors.lastname: Goodspeed
authors.forename: Shari
authors.initials: S
authors.lastname: Wang
authors.forename: Mohamed
authors.initials: M
authors.lastname: Omer
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Den Hartigh
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Averill
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ledbetter
authors.forename: Alan
authors.initials: A
authors.lastname: Chait
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D000818:Animals; D023201:CD40 Ligand / Q000037:antagonists & inhibitors / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D059305:Diet, High-Fat; D007136:Immunoglobulins / Q000008:administration & dosage*; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007333:Insulin Resistance / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology / Q000473:pathology*; D015430:Weight Gain / Q000187:drug effects / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D007136:Immunoglobulins; D023201:CD40 Ligand