Circulating CD4 CD25CD127 Regulatory T-Cell Levels Do Not Reflect the Extent or Severity of Carotid and Coronary Atherosclerosis

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). Conclusion—The results suggest that determination of circulating Treg-cell levels based on flow cytometry or mRNA assessment is not a useful indicator of the extent or severity of atherosclerosis. 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 lym-phocytes (ie, CD69 ϩ , HLA-DR ϩ , and CD 137 ϩ T cells) in peripheral blood in particular during acute coronary syndromes (ACSs). 2– 4 On the other hand, regulatory T (Treg) cells reduce the development of experimental atherosclerosis acting both systemically and within the lesion. 5,6 Immuno-staining 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 …