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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:893.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Role of Naturally Occurring CD4⁺CD25⁺ Regulatory T Cells in Experimental Atherosclerosis

Adi Mor; David Planer; Galia Luboshits; Arnon Afek; Shula Metzger; Tova Chajek-Shaul; Gad Keren; Jacob George

From the Department of Cardiology (A.M., G.L., A.A., G.K., J.G.), Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, and the Department of Medicine (D.P., S.M., T.C.-S.), Hadassah University Hospital, Mount Scopus, Israel.

Correspondence and reprint requests to Jacob George, MD, Department of Cardiology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. E-mail jacobg{at}post.tau.ac.il

Objective— Naturally occurring CD4⁺CD25⁺ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis.

Methods and Results— Tregs were investigated comparatively between aged and young apolipoprotein E–knockout (ApoE-KO) mice and age-matched C57BL/6 littermates. The effect of oxidized LDL (oxLDL) was tested on the functional suppressive properties of Tregs from ApoE-KO and C57BL/6 mice. Tregs, CD4⁺CD25^– cells, and saline were infused into ApoE-KO mice to study their effects on atherogenesis. Treg numbers were reduced in atherosclerotic compared with nonatherosclerotic ApoE-KO mice. The functional suppressive properties of Tregs from ApoE-KO mice were compromised in comparison with those from their C57BL/6 littermates. Thus, oxLDL attenuated the suppressive properties of Tregs from C57BL/6 mice and more so in ApoE-KO mice. Transfer of Tregs from age-matched ApoE-KO mice resulted in significant attenuation of atherosclerosis compared with that after delivery of CD4⁺CD25^+/– T cells or phosphate-buffered saline.

Conclusions— CD4⁺CD25⁺ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.

Naturally occurring CD4⁺CD25⁺ regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis. CD4⁺CD25⁺ Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.

Key Words: atherosclerosis • T cells • immune response • adoptive transfer • foxp3

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