Role of Naturally Occurring CD4 + CD25 + Regulatory T Cells in Experimental Atherosclerosis
- 1 April 2007
- journal article
- research article
- Published by Wolters Kluwer Health in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 27 (4), 893-900
- https://doi.org/10.1161/01.atv.0000259365.31469.89
Abstract
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.Keywords
This publication has 32 references indexed in Scilit:
- Inflammation, Atherosclerosis, and Coronary Artery DiseaseNew England Journal of Medicine, 2005
- In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune DiabetesThe Journal of Experimental Medicine, 2004
- Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with $beta;2-glycoprotein ICardiovascular Research, 2004
- Human CD4+CD25+ regulatory T cellsSeminars in Immunology, 2004
- Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritisEuropean Journal of Immunology, 2003
- Inflammation in atherosclerosisNature, 2002
- Innate and acquired immunity in atherogenesisNature Medicine, 2002
- Mucosal Administration of Heat Shock Protein-65 Decreases Atherosclerosis and Inflammation in Aortic Arch of Low-Density Lipoprotein Receptor-Deficient MiceCirculation, 2002
- Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune EncephalomyelitisScience, 1994
- Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cellsCell, 1992