Expansion of CD4 1 CD28 null T-lymphocytes in diabetic patients: exploring new pathogenetic mechanisms of increased cardiovascular risk in diabetes mellitus

Diabetes mellitus (DM) is associated with high incidence of first and recurrent cardiovascular events, especially acute coronary syndromes (ACSs); however, the mechanisms involved are still unknown. We sought to investigate the role of CD4 + CD28 null T-lymphocytes, a rare long-lived subset of T-lymphocytes with proatherogenic and plaque-destabi-lizing properties, in the increased cardiovascular risk associated with DM. the 36-month event-free survival was the lowest in those with DM and CD4 + CD28 null T-cells ≥ 4% and highest in those without DM and CD4 + CD28 null T-cells , 4% ( P , 0.001), being intermediate in those with only one of these features. Conclusions In DM patients, CD4 + CD28 null T-cells are expanded and are associated with poor glycaemic control; they also correlate with the occurrence of a first cardiovascular event and with a worse outcome after an ACS. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords

[1]  P. O S I T I O N S T A T E M E N T,et al.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[2]  R. Goldberg.  Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. , 2009, The Journal of clinical endocrinology and metabolism.

[3]  D. Levy,et al.  Trends in All-Cause and Cardiovascular Disease Mortality Among Women and Men With and Without Diabetes Mellitus in the Framingham Heart Study, 1950 to 2005 , 2009, Circulation.

[4]  J. Plutzky,et al.  The pathologic continuum of diabetic vascular disease. , 2009, Journal of the American College of Cardiology.

[5]  G. Niccoli,et al.  Different apparent prognostic value of hsCRP in type 2 diabetic and nondiabetic patients with acute coronary syndromes. , 2009, Clinical chemistry.

[6]  J. Kaski,et al.  Differential Pathways Govern CD4+CD28− T Cell Proinflammatory and Effector Responses in Patients with Coronary Artery Disease , 2008, The Journal of Immunology.

[7]  Christopher P Cannon,et al.  Diabetes and mortality following acute coronary syndromes. , 2007, JAMA.

[8]  A. Rebuzzi,et al.  Unusual CD4+CD28null T lymphocytes and recurrence of acute coronary events. , 2007, Journal of the American College of Cardiology.

[9]  Ann Marie Schmidt,et al.  Advanced glycation end products: sparking the development of diabetic vascular injury. , 2006, Circulation.

[10]  A. Rebuzzi,et al.  Modulation of CD4+CD28null T Lymphocytes by Tumor Necrosis Factor-&agr; Blockade in Patients With Unstable Angina , 2006, Circulation.

[11]  Kayoko Sato,et al.  T Cell Recognition and Killing of Vascular Smooth Muscle Cells in Acute Coronary Syndrome , 2006, Circulation research.

[12]  J. Fernández-Real,et al.  Burden of infection and insulin resistance in healthy middle-aged men. , 2006, Diabetes care.

[13]  R. Frye,et al.  Interleukin 12 Induces T-Cell Recruitment Into the Atherosclerotic Plaque , 2006, Circulation research.

[14]  R. Frye,et al.  TRAIL-expressing T cells induce apoptosis of vascular smooth muscle cells in the atherosclerotic plaque , 2006, The Journal of experimental medicine.

[15]  R. Simó,et al.  CD4-CD8 and CD28 expression in T cells infiltrating the vitreous fluid in patients with proliferative diabetic retinopathy: a flow cytometric analysis. , 2004, Archives of ophthalmology.

[16]  S. Wild,et al.  Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. , 2004, Diabetes care.

[17]  Qingbo Xu,et al.  Heat-Shock Protein 60-Reactive CD4+CD28null T Cells in Patients With Acute Coronary Syndromes , 2004, Circulation.

[18]  A. Vallejo,et al.  T-cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection. , 2004, Trends in molecular medicine.

[19]  J. Pickup,et al.  Activation of the innate immune system as a predictor of cardiovascular mortality in Type 2 diabetes mellitus , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[20]  P. Macfarlane,et al.  Metabolic Syndrome With and Without C-Reactive Protein as a Predictor of Coronary Heart Disease and Diabetes in the West of Scotland Coronary Prevention Study , 2003, Circulation.

[21]  A. Vallejo,et al.  CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation. , 2003, Blood.

[22]  AntonioCeriello,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans , 2002 .

[23]  R. Marfella,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress , 2002, Circulation.

[24]  Peter Libby,et al.  Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. , 2002, JAMA.

[25]  R. Frye,et al.  T-Cell–Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes , 2002, Circulation.

[26]  A. Vallejo,et al.  Down-Regulation of CD28 Expression by TNF-α1 , 2001, The Journal of Immunology.

[27]  J. Manson,et al.  C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. , 2001, JAMA.

[28]  R. Frye,et al.  Molecular Fingerprint of Interferon-&ggr; Signaling in Unstable Angina , 2001, Circulation.

[29]  S. Yusuf,et al.  Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non–Q-Wave Myocardial Infarction: Results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry , 2000, Circulation.

[30]  R. Frye,et al.  Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes. , 2000, Circulation.

[31]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[32]  R. Frye,et al.  Perturbation of the T-cell repertoire in patients with unstable angina. , 1999, Circulation.

[33]  D. Schaid,et al.  Expansion of unusual CD4+ T cells in severe rheumatoid arthritis. , 1997, Arthritis and rheumatism.

[34]  L. Wilhelmsen,et al.  Stroke trends in the WHO MONICA project. , 1997, Stroke.