Abstract 12971: A Novel Combination Therapy with Anti-CD3 Antibody and IL-2 Complexes Against Atherosclerosis Targeting Effector T Cells and Regulatory T Cells

Background: Accumulating evidence suggests that a balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for the control of atherosclerotic disease. We hypothesized that combination therapy with anti-CD3 antibody (CD3-Ab) and IL-2/anti-IL-2 monoclonal antibody complexes (IL-2 complexes) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. Methods and results: We treated eight-week old apolipoprotein E-deficient mice fed a high fat diet with vehicle (untreated) (n=10), CD3-Ab (50μg/day) (n=11), IL-2 complexes (1 μg recombinant IL-2 plus 5 μg anti-IL-2 mAb per day) (n=12) and their combination (CD3-Ab + IL-2 complexes) (n=11). Flow cytometric analysis of immune cells was performed at 10 weeks of age and atherosclerosis was assessed at 16 weeks old. CD3-Ab monotherapy moderately reduced atherosclerotic lesion formation (aortic sinus mean plaque area: 62.0±2.8х104 to 53.8±2.3х104 μm2, p≤0.05) compared with untreated con...