Open AccessCD 3 Antibody and IL ‐2 Complex Combination Therapy Inhibits Atherosclerosis by Augmenting a Regulatory Immune Response
Author(s) -
Kasahara Kazuyuki,
Sasaki Naoto,
Yamashita Tomoya,
Kita Tomoyuki,
Yodoi Keiko,
Sasaki Yoshihiro,
Takeda Masafumi,
Hirata Kenichi
Publication year - 2014
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000719
Subject(s) - medicine , immune system , antibody , immunology , monoclonal antibody , macrophage , effector , combination therapy , inflammation , in vitro , biology , biochemistry
Background Accumulating evidence suggests that the balance between pathogenic effector T cells (Teffs) and regulatory T cells (Tregs) may be important for controlling atherosclerotic disease. We hypothesized that a combination therapy with anti‐ CD 3 antibody ( CD 3‐Ab) and IL ‐2/anti‐ IL ‐2 monoclonal antibody complex ( IL ‐2 complex) aimed at increasing the ratio of Tregs to Teffs would effectively inhibit atherosclerosis in mice. Methods and Results We treated apolipoprotein E‐deficient mice fed a high‐cholesterol diet with vehicle, CD 3‐Ab, IL ‐2 complex, or their combination. Mice receiving the combination therapy had markedly reduced atherosclerotic lesions than mice treated with CD 3‐Ab or IL ‐2 complex alone. In addition, a striking increase in the Treg/Teff ratio of lymphoid organs and atherosclerotic lesions, along with plaque stabilization characterized by decreased macrophage content and increased collagen content was observed. The combination treatment also markedly reduced splenic Ly6C high inflammatory monocytes and might induce a favorable macrophage phenotype change in atherosclerotic lesions. Conclusions Our results indicate that in addition to suppressing Teff responses, enhancing Treg‐mediated immune responses is more efficacious in preventing atherosclerosis, suggesting a novel therapeutic approach for atherosclerosis.