title: Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.
abstract: OBJECTIVE
  T cells, particularly CD8(+) T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8(+) T-cell accumulation and activation in AT and the role of CD11a, a β2 integrin.
  
  
  RESULTS
  CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression. In vitro, CD8(+) T cells from mouse AT displayed increased interferon-γ expression and proliferation to stimulation with interleukin-12 and interleukin-18, which were increased in obese AT. CD11a was upregulated in CD8(+) T cells in obese mice. Ablation of CD11a in obese mice dramatically reduced T-cell accumulation, activation, and proliferation in AT. Adoptive transfer showed that CD8(+) T cells from wild-type mice, but not from CD11a-deficient mice, infiltrated into AT of recipient obese wild-type mice. CD11a deficiency also reduced tumor necrosis factor-α-producing and interleukin-12-producing macrophages in AT and improved insulin resistance.
  
  
  CONCLUSIONS
  Combined action of cytokines in obese AT induces proliferative response of CD8(+) T cells locally, which, along with increased infiltration, contributes to CD8(+) T-cell accumulation and activation in AT. CD11a plays a crucial role in AT inflammation by participating in T-cell infiltration and activation.
authors.affiliation: From the Departments of Medicine (E.J., X.D.P., D.Y., I.M.K., J.L.P., C.M.B., H.W.) and Pediatrics (C.W.S., C.M.B., H.W.), Baylor College of Medicine, Houston, TX; and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, The Methodist Hospital, Houston, TX (C.M.B.).
authors.forename: Erlie
authors.initials: E
authors.lastname: Jiang
authors.forename: Xiaoyuan Dai
authors.initials: XD
authors.lastname: Perrard
authors.forename: Donglin
authors.initials: D
authors.lastname: Yang
authors.forename: Ilvira M
authors.initials: IM
authors.lastname: Khan
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Perrard
authors.forename: C Wayne
authors.initials: CW
authors.lastname: Smith
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Huaizhu
authors.initials: H
authors.lastname: Wu
mesh_terms: D000273:Adipose Tissue / Q000276:immunology*; D019264:Adoptive Transfer; D000818:Animals; D040881:CD11a Antigen / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015434:Panniculitis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015430:Weight Gain
chemical_list: D040881:CD11a Antigen; D018836:Inflammation Mediators; D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: adipose tissue; inflammation; insulin resistance; obesity