Circulating CD4+ CD25hiCD127lo Regulatory T-Cell Levels Do Not Reflect the Extent or Severity of Carotid and Coronary Atherosclerosis

被引:131
作者
Ammirati, Enrico [1 ,10 ]
Cianflone, Domenico [1 ]
Banfi, Michela [1 ]
Vecchio, Viviana [2 ]
Palini, Alessio [2 ]
De Metrio, Monica [4 ]
Marenzi, Giancarlo [4 ]
Panciroli, Claudio [9 ]
Tumminello, Gabriele [9 ]
Anzuini, Angelo [5 ]
Palloshi, Altin [5 ]
Grigore, Liliana [6 ]
Garlaschelli, Katia [6 ]
Tramontana, Simona [6 ]
Tavano, Davide [8 ]
Airoldi, Flavio [8 ]
Manfredi, Angelo A. [3 ]
Catapano, Alberico Luigi [6 ,7 ,8 ]
Norata, Giuseppe Danilo [6 ,7 ]
机构
[1] Ist Sci San Raffaele, Clin Cardiovasc Biol Ctr, Clin Immunol Unit, I-20132 Milan, Italy
[2] Ist Sci San Raffaele, Flow Cytometry Resource Analyt Cytol Tech Applica, Clin Immunol Unit, I-20132 Milan, Italy
[3] Univ Vita Salute San Raffaele, I-20132 Milan, Italy
[4] Univ Milan, Dept Cardiovasc Sci, IRCCS, Ctr Cardiol Monzino, Milan, Italy
[5] Ist Clin Citta Studi, Milan, Italy
[6] Bassini Hosp Cinisello Balsamo, Ctr Study Atherosclerosis, Italian Soc Study Atherosclerosis Lombardia Chapt, Milan, Italy
[7] Univ Milan, Dept Pharmacol Sci, Milan, Italy
[8] Multimed IRCCS, Intervent Cardiol Unit, Milan, Italy
[9] Azienda Osped Prov Lodi, Intervent Cardiol Unit, Lodi, Italy
[10] Heart Care Fdn, Florence, Italy
关键词
regulatory T cells; coronary artery disease; flow cytometry; carotid artery intima-media thickness; acute coronary syndrome; MEDIA THICKNESS; EXPRESSION; EFFECTOR; FOXP3; COSTIMULATION; INFLAMMATION; VACCINATION; ACTIVATION; MECHANISMS; IMMUNITY;
D O I
10.1161/ATVBAHA.110.206813
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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(+) 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). 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. (Arterioscler Thromb Vasc Biol. 2010; 30: 1832-1841.)
引用
收藏
页码:1832 / U359
页数:37
相关论文
共 49 条
[41]   Cytokine profiles and T cell function in acute coronary syndromes [J].
Steppich, Birgit A. ;
Moog, Philipp ;
Matissek, Christoph ;
Wisniowski, Nicola ;
Kuehle, Jan ;
Joghetaei, Nader ;
Neumann, Franz-Josef ;
Schomig, Albert ;
Ott, Ilka .
ATHEROSCLEROSIS, 2007, 190 (02) :443-451
[42]  
STEWART CC, 1994, METHOD CELL BIOL, V41, P61
[43]   Vaccination against Foxp3+ regulatory T cells aggravates atherosclerosis [J].
van Es, T. ;
van Puijvelde, G. H. M. ;
Foks, A. C. ;
Habets, K. L. L. ;
Bot, I. ;
Gilboa, E. ;
Van Berkel, T. J. C. ;
Kuiper, J. .
ATHEROSCLEROSIS, 2010, 209 (01) :74-80
[44]   Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis [J].
van Puijvelde, G. H. M. ;
Hauer, A. D. ;
de Vos, P. ;
van den Heuvel, R. ;
van Herwijnen, M. J. C. ;
van der Zee, R. ;
van Eden, W. ;
van Berkel, T. J. C. ;
Kuiper, J. .
CIRCULATION, 2006, 114 (18) :1968-1976
[45]   Mechanisms of suppression by suppressor T cells [J].
von Boehmer, H .
NATURE IMMUNOLOGY, 2005, 6 (04) :338-344
[46]   Atheroprotective Effects of Alum Are Associated With Capture of Oxidized LDL Antigens and Activation of Regulatory T Cells [J].
Wigren, Maria ;
Bengtsson, Daniel ;
Duner, Pontus ;
Olofsson, Katarina ;
Bjorkbacka, Harry ;
Bengtsson, Eva ;
Fredrikson, Gunilla Nordin ;
Nilsson, Jan .
CIRCULATION RESEARCH, 2009, 104 (12) :E62-E70
[47]   Critical role for CCR5 in the function of donor CD4+CD25+ regulatory T cells during acute graft-versus-host disease [J].
Wysocki, CA ;
Jiang, Q ;
Panoskaltsis-Mortari, A ;
Taylor, PA ;
McKinnon, KP ;
Su, LS ;
Blazar, BR ;
Serody, JS .
BLOOD, 2005, 106 (09) :3300-3307
[48]   CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence [J].
Yurchenko, Ekaterina ;
Tritt, Michael ;
Hay, Valerie ;
Shevach, Ethan M. ;
Belkaid, Yasmine ;
Piccirillo, Ciriaco A. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (11) :2451-2460
[49]   Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes [J].
Zal, B ;
Kaski, JC ;
Arno, G ;
Akiyu, JP ;
Xu, QB ;
Cole, D ;
Whelan, M ;
Russell, N ;
Madrigal, JA ;
Dodi, IA ;
Baboonian, C .
CIRCULATION, 2004, 109 (10) :1230-1235