Differential effects of regulatory T cells on the initiation and regression of atherosclerosis
2011
Foks, A.C. | Frodermann, V. | ter Borg, M. | Habets, K.L.L. | Bot, I. | Zhao, Y. | van Eck, M. | van Berkel, Th.J.C. | Kuiper, J. | van Puijvelde, G.H.M.
OBJECTIVE: Regulatory T cells (Tregs) play an important role in the regulation of T cell-mediated immune responses through suppression of T cell proliferation and cytokine production. In atherosclerosis, a chronic autoimmune-like disease, an imbalance between pro-inflammatory cells (Th1/Th2) and anti-inflammatory cells (Tregs) exists. Therefore, increased Treg numbers may be beneficial for patients suffering from atherosclerosis. In the present study, we determined the effect of a vast expansion of Tregs on the initiation and regression of well-established lesions. METHODS AND RESULTS: For in vivo Treg expansion, LDL receptor deficient (LDLr⁻/⁻) mice received repeated intraperitoneal injections of a complex of IL-2 and anti-IL-2 mAb. This resulted in a 10-fold increase in CD4⁺CD25ʰⁱFoxp3⁺ T cells, which potently suppressed effector T cells ex vivo. During initial atherosclerosis, IL-2 complex treatment of LDLr⁻/⁻ mice fed a Western-type diet reduced atherosclerotic lesion formation by 39%. The effect on pre-existing lesions was assessed by combining IL-2 complex treatment with a vigorous lowering of blood lipid levels in LDLr⁻/⁻ mice. This did not induce regression of atherosclerosis, but significantly enhanced lesion stability. CONCLUSION: Our data show differential roles for Tregs during atherosclerosis: Tregs suppress inflammatory responses and attenuate initial atherosclerosis development, while during regression Tregs can improve stabilization of the atherosclerotic lesions.
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