Oral Anti-CD3 Antibody Treatment Induces Regulatory T Cells and Inhibits the Development of Atherosclerosis in Mice

Article

关键词: GROWTH-FACTOR-BETA;    TRANSCRIPTION FACTOR FOXP3;    NITRIC-OXIDE SYNTHASE;    TGF-BETA;    DEFICIENT MICE;    ACCELERATES ATHEROSCLEROSIS;    CD3-SPECIFIC ANTIBODY;    MONOCLONAL-ANTIBODY;    DIABETES-MELLITUS;    LESION FORMATION;   

DOI  :  10.1161/CIRCULATIONAHA.109.863431

来源: SCIE

【 摘 要 】

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. Methods and 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. (Circulation. 2009; 120: 1996-2005.)

【 授权许可】

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