title: CD3 antibody and IL-2 complex combination therapy inhibits atherosclerosis by augmenting a regulatory immune response.
abstract: BACKGROUND
  Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti-CD3 antibody (CD3-Ab) and IL-2/anti-IL-2 monoclonal antibody complex (IL-2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice.
  
  
  RESULTS
  We treated apolipoprotein E-deficient mice fed a high-cholesterol diet with vehicle, CD3-Ab, IL-2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD3-Ab or IL-2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C(high) inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions.
  
  
  CONCLUSIONS
  Our results indicate that in addition to suppressing Teff responses, enhancing Treg-mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Keiko
authors.initials: K
authors.lastname: Yodoi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001018:Aortic Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D017252:CD3 Complex / Q000276:immunology*; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007111:Immunity, Cellular / Q000187:drug effects; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001057:Apolipoproteins E; D017252:CD3 Complex; D002791:Cholesterol, Dietary; D007376:Interleukin-2
keywords: T cell; atherosclerosis; immune system; inflammation
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