title: Oral anti-CD3 antibody treatment induces regulatory T cells and inhibits the development of atherosclerosis in mice.
abstract: BACKGROUND
  Accumulating evidence suggests that several subsets of regulatory T cells that actively mediate immunologic tolerance play crucial roles in atherogenesis. Recently, orally administered anti-CD3 monoclonal antibody has been shown as an inducer of novel regulatory T cells expressing latency-associated peptide (LAP) on their surface, which potently prevents systemic autoimmunity. In the present study, we hypothesized that oral anti-CD3 antibody treatment may inhibit atherosclerosis in mice.
  
  
  RESULTS
  Six-week-old apolipoprotein E-deficient mice on a standard diet were orally given anti-CD3 antibody or control immunoglobulin G on 5 consecutive days, and atherosclerosis was assessed at age 16 weeks. Oral administration of anti-CD3 antibody significantly reduced atherosclerotic lesion formation and accumulations of macrophages and CD4(+) T cells in the plaques compared with controls. We observed a significant increase in LAP(+) cells and CD25(+)Foxp3(+) cells in the CD4(+) T-cell population in anti-CD3-treated mice, in association with increased production of the antiinflammatory cytokine transforming growth factor-beta and suppressed T-helper type 1 and type 2 immune responses. Neutralization of transforming growth factor-beta in vivo abrogated the preventive effect of oral anti-CD3 antibody.
  
  
  CONCLUSIONS
  Our findings indicate the atheroprotective role of oral anti-CD3 antibody treatment in mice via induction of a regulatory T-cell response. These findings suggest that oral immune modulation may represent an attractive therapeutic approach to atherosclerosis.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakajima
authors.forename: Hideto
authors.initials: H
authors.lastname: Tawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Usui
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity / Q000187:drug effects; D017252:CD3 Complex / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D017252:CD3 Complex; D016212:Transforming Growth Factor beta