Differential effects of regulatory T cells on the initiation and regression of atherosclerosis
| Autor: | Kim L. L. Habets, G.H.M. van Puijvelde, Johan Kuiper, Vanessa Frodermann, Amanda C. Foks, Th.J.C. van Berkel, Ying Zhao, M. Van Eck, M. ter Borg, Ilze Bot |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_specialty medicine.medical_treatment T cell Autoimmunity Mice Transgenic chemical and pharmacologic phenomena Inflammation Biology T-Lymphocytes Regulatory Mice Th2 Cells Immune system Internal medicine medicine Animals IL-2 receptor Interleukin-2 Receptor alpha Subunit FOXP3 Forkhead Transcription Factors Th1 Cells Atherosclerosis Treatment Outcome Endocrinology Cytokine medicine.anatomical_structure Gene Expression Regulation Immunology LDL receptor Interleukin-2 medicine.symptom Cardiology and Cardiovascular Medicine Ex vivo |
| Zdroj: | Atherosclerosis. 218:53-60 |
| ISSN: | 0021-9150 |
| Popis: | 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 + CD25 hi Foxp3 + 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. |
| Databáze: | OpenAIRE |
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