title: Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice.
abstract: OBJECTIVE
  Although recent animal studies have investigated the cellular and molecular mechanisms underlying the process of atherosclerosis regression, it remains unknown whether adaptive immune responses including T cells are involved in this process. We investigated the role of T cells in atherosclerosis regression.
  
  
  RESULTS
  LDL receptor-deficient mice were fed a high-cholesterol diet for 8 weeks to form atherosclerotic lesions and were then changed to a standard diet, and atherosclerosis was assessed 4 weeks later. Just before changing the diet, the mice received an iv injection of anti-CD3 antibody (CD3-Ab) or control immunoglobulin G for 5 consecutive days. CD3-Ab treatment regressed atherosclerosis and decreased the accumulation of macrophages and CD4(+) T cells in the plaques. CD3-Ab treatment also dramatically reduced CD4(+) T cells and increased the proportion of regulatory T cells (Tregs). Depletion of Tregs by anti-CD25 antibody injection abolished the regression of atherosclerosis seen in CD3-Ab-treated mice, indicating the essential role for Tregs in this process.
  
  
  CONCLUSIONS
  CD3-Ab treatment induced rapid regression of established atherosclerosis via reducing CD4(+) T cells and increasing the proportion of Tregs. These findings suggest that therapeutic intervention for T-cell-mediated immune responses may represent a novel strategy to induce atherosclerosis regression in combination with lipid-lowering therapy.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kita
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kasahara
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Keiko
authors.initials: K
authors.lastname: Yodoi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017252:CD3 Complex; C456519:visilizumab
keywords: Atherosclerosis; Inflammation; Lymphocytes; Regression; Regulatory T-cell