Abstract 15183: Effector T Cell Suppression Using Anti-CD3 Antibody Induces the Regression of Established Atherosclerosis in Mice

Background: Although recent clinical trials demonstrated that regression of atherosclerosis is achieved in human, the mechanisms of atherosclerosis regression are not fully elucidated. Anti-CD3 antibody (CD3-Ab) is an immunosuppressive agent and is reported to inhibit atherosclerosis. Intravenous injection of CD3-Ab dramatically decreased CD4 + effector T cells, while its oral administration increased regulatory T cells (Tregs), and each of them contributes towards preventing atherosclerosis. The present study tested the hypothesis that treatment of CD3-Ab will induce regression of existing atherosclerotic lesions in mice. Methods and Results: We set up a new atherosclerosis regression model using LDL-receptor deficient mice. After 8 weeks exposure of high cholesterol diet, the diet was changed to normal chow at 14 weeks of age and kept for 4 weeks. We confirmed that there is no significant change in the atherosclerotic lesion size at aortic root by only changing the chow. However, intravenous administration of CD3-Ab in addition to normalizing plasma cholesterol significantly regressed atherosclerotic lesions (4.90±0.26×10 5 μm 2 , P 5 μm 2 ). Intravenous administration of CD3-Ab markedly decreased the number of CD4 + effector T cells (−53.3% vs. control). Oral administration of CD3-Ab never affected the atherosclerotic lesion size at aortic root though Tregs were significantly increased. Conclusions: Intravenous CD3-Ab therapy induces the regression of established atherosclerosis via dramatic reduction of CD4 + effector T cells. These results implied the possibility that the intervention to the number and function of effector T cells could be a hopeful therapy to achieve the regression of atherosclerosis.