Objective-Regulatory T (Treg) cells play a protective role in experimental atherosclerosis. In the present study, we investigated whether the levels of circulating Treg cells relate to the degree of atherosclerosis in carotid and coronary arteries. Methods and Results-We studied 2 distinct populations: (1) 113 subjects, selected from a free-living population (carotid study), in which we measured the intima-media thickness of the common carotid artery, as a surrogate marker of initial atherosclerosis; and (2) 75 controls and 125 patients with coronary artery disease (coronary study): 36 with chronic stable angina, 50 with non-ST-elevation acute coronary syndrome, 39 with ST-elevation acute myocardial infarction. Treg-cell levels were evaluated by flow cytometry (Treg cells identified as CD3 ϩ CD4 ϩ CD25 high CD127 low ) and by mRNA expression of forkhead box P3 or of Treg-associated cytokine interleukin 10. In the carotid study, no correlation was observed between Treg-cell levels and intima-media thickness. No differences in Treg-cell levels were observed comparing rapid versus slow intima-media thickness progressors from a subgroup of patients (nϭ65), in which prospective data on 6-year intima-media thickness progression were available. In the coronary group, Treg-cell levels were not altered in chronic stable angina patients. In contrast, nonunivocal variations were observed in patients suffering an acute coronary syndrome (with a Treg-cell increase in ST-elevation acute myocardial infarction and a Treg-cell decrease in non-ST-elevation acute coronary syndrome patients). Key Words: regulatory T cells Ⅲ coronary artery disease Ⅲ flow cytometry Ⅲ carotid artery intima-media thickness Ⅲ acute coronary syndrome T cells play a role in atherosclerosis and in acute manifestation of plaque destabilization. 1 The activation of inflammatory pathways in atherosclerosis and in coronary artery disease (CAD) is not confined to coronary lesions but involves the activation of neutrophils, monocytes, and lymphocytes (ie, CD69 Conclusion-Theϩ , HLA-DR ϩ , and CD 137 ϩ T cells) in peripheral blood in particular during acute coronary syndromes (ACSs). [2][3][4] On the other hand, regulatory T (Treg) cells reduce the development of experimental atherosclerosis acting both systemically and within the lesion. 5,6 Immunostaining of human atherosclerotic plaques showed that Treg cells are present during all stages of plaque development in the intima and adventitia. 7 In general, Treg cells play a key role in the maintenance of immunologic self-tolerance and negative control of a variety of pathological immune responses. 8 Several subsets of Treg cells with distinct phenotypes and distinct mechanisms of action have been described (see Sakaguchi et al,8 Roncarolo et al, 9 and O'Garra and Vieira 10 for review). Treg cells mediate the immunoregulatory function by producing cytokines, such as interleukin (IL)-10 and See accompanying article on page 1679 ϩ Treg cells, which have increased ability of homing and trafficking to inflamed nonly...

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OBJECTIVE -Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS -We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twentyfive patients did not receive a functioning islet transplant (kidney-only group).RESULTS -GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 Ϯ 3.5% at baseline to 74.9 Ϯ 2.1% at 3 years posttransplantation, P Ͻ 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 Ϯ 0.25 to 4.20 Ϯ 0.37 EDV/s, P Ͻ 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P Ͻ 0.05). The kidneyislet group also showed a reduction of both QT dispersion (53.5 Ϯ 4.9 to 44.6 Ϯ 2.9 ms, P Ͻ 0.05) and corrected QT (QTc) dispersion (67.3 Ϯ 8.3 to 57.2 Ϯ 4.6 ms, P Ͻ 0.05) with higher erythrocytes Na ϩ -K ϩ -ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness.CONCLUSIONS -Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft. Diabetes Care 28:1358 -1365, 2005M ost cardiac disease and events in type 1 diabetic patients are due to 1) diabetic cardiomyopathy, with progressive deterioration of left ventricular function; 2) diabetic coronary angiopathy, with progression of coronary atherosclerosis; or 3) diabetic sudden death resulting from myocyte electrical failure (1-3).With diabetic cardiomyopathy, systolic dysfunction in normotensive diabetic patients has not been clearly shown (3). Abnormality in diastolic dysfunction has been uniformly observed in asymptomatic diabetic patients, but its relationship with metabolic control in type 1 diabetic patients is still a matter of debate (4 -6).With diabetic coronary angiopathy, progressive worsening of coronary artery atherosclerosis and macroangiopathy is evident in patients with diabetes, but pancreas and islet transplants reduce this risk (7-11). A noninvasive marker of atherosclerosis and coronary events is intimamedia thickness (IMT) (12), which is stabil...

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