Circulating CD4+CD25hiCD127lo 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.


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(+)CD4(+)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 (n=65), 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).


CONCLUSIONS
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.
Clinical Cardiovascular Biology Research Centre, San Raffaele Scientific Institute and the Università Vita-Salute San Raffaele, Via Olgettina 58, 20132 Milan, Italy. ammirati.enrico@hsr.it
Enrico
E
Ammirati
Domenico
D
Cianflone
Michela
M
Banfi
Viviana
V
Vecchio
Alessio
A
Palini
Monica
M
De Metrio
Giancarlo
G
Marenzi
Claudio
C
Panciroli
Gabriele
G
Tumminello
Angelo
A
Anzuini
Altin
A
Palloshi
Liliana
L
Grigore
Katia
K
Garlaschelli
Simona
S
Tramontana
Davide
D
Tavano
Flavio
F
Airoldi
Angelo A
AA
Manfredi
Alberico Luigi
AL
Catapano
Giuseppe Danilo
GD
Norata
D054058:Acute Coronary Syndrome / Q000276:immunology; D000368:Aged; D000787:Angina Pectoris / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000276:immunology*; D016022:Case-Control Studies; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000097:blood; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014463:Ultrasonography
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D053699:Interleukin-7 Receptor alpha Subunit; D012333:RNA, Messenger; D016753:Interleukin-10