Changes of CD4⁺CD25⁺ regulatory T cells in patients with acute coronary syndrome and the effects of atorvastatin

Abstract

The function of CD4⁺CD25⁺ regulatory T lymphocytes (Treg) in patients with acute coronary syndrome (ACS) and the effects of atorvastatin were investigated. Forty-eight patients with ACS were randomly divided into two groups: group C receiving conventional therapy (n=24), and group C+A receiving conventional therapy+atorvastatin (10 mg/day, n=24). T lymphocytes from ACS patients (before and 2 weeks after the treatment) or 18 healthy subjects were separated and the flow cytometry was used to measure the percentage of Treg. The inhibitory ability of Treg on effector T cells was determined by mixed lymphocyte reaction (MLR). ELISA was used to measure the serum levels of cytokines (IL-10, TGF-β1 and IFN-γ) before and after treatment. The results showed that as compared with normal control group, Treg percentage was decreased significantly (P<0.01), the inhibitory ability of Treg on the T lymphocytes proliferation was reduced (P<0.01), IFN-γ levels were increased and IL-10 and TGF-β1 levels were lowered in ACS patients. After treatment with atorvastatin, Treg percentage and the inhibitory ability of Treg on T lymphocytes proliferation were significantly increased in ACS patients. Serum IFN-γ was decreased significantly, while IL-10 and TGF-β1 were elevated significantly as compared with the non-atorvastatin group. The number of Treg was positively correlated with serum TGF-β1, but negatively with serum IFN-γ and CRP. It was concluded that ACS was associated with decreased number and defected function of Treg, which may play an important role in initiating immune-inflammatory response in ACS. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on Treg and restoration of immune homeostasis.

Keywords

acute coronary syndrome / regulatory CD4⁺CD25⁺ T lymphocytes / cytokine / atorvastatin

References

[1] RanjitS., LiD. Z., ZengQ. T., et al.. Differentiation of dendritic cells in monocyte cultures isolated from patients with unstable angina pectoris. Int J Cardiol, 2004, 97(3): 551-556

[2] LiD. Z., RanjitS., WuW., et al.. Dendritic cell mediated heat-shock protein 60 specific T cytotoxicity in acute coronary syndrome. Chin Ciucu J (Chinese), 2005, 5: 340-343

[3] SakaguchiS., SakaguchiN.. Regulatory T cells in immunologic self-tolerance and autoimmune disease. Int Rev Immunol, 2005, 24(3–4): 211-226

[4] LiD. Z., RanjitS., ZengQ. T., et al.. Effects of atorvastatin on the function of dendritic cells in patients with unstable angina pectoris. Chin J Intern Med (Chinese), 2004, 6: 429-432

[5] FehrT., KahlertC., FierzW., et al.. Statin-induced immunomodulatory effects on human T cells in vivo. Atherosclerosis, 2004, 175(1): 83-90

[6] HoshildaS., NishinoM., TanouchiJ., et al.. Acute Chlamydia pneumoniae infection with heat shock protein 60-related response in patients with acute coronary syndrome. Atherosclerosis, 2005, 183(1): 109-112

[7] BacchettaR., GregoriS., RoncaroloM. G., et al.. CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev, 2005, 4(8): 491-496

[8] MallatZ., Ait-OufellaH., TedguiA.. Regulatory T cell responses: potential role in the control of atherosclerosis. Curr Opin Lipidol, 2005, 16(5): 518-524

[9] VerginisP., LiH. S., CarayanniotisG.. Tolerogenic semimature dendritic cells suppress experimental autoimmune thyroiditis by activation of thyroglobulin-specific CD4+ CD25+ T cells. J Immunol, 2005, 174(11): 7433-7439