Circulating CD4+CD25hiCD127lo regulatory T-cell levels do not reflect the extent or severity of carotid and coronary atherosclerosis

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 30, Issue 9, 2010, Pages 1832-1841

  Ammirati, Enrico ^a,g   Cianflone, Domenico ^a   Banfi, Michela ^a   Vecchio, Viviana ^a   Palini, Alessio ^a   De Metrio, Monica ^b   Marenzi, Giancarlo ^b   Panciroli, Claudio ^f   Tumminello, Gabriele ^f   Anzuini, Angelo ^c   Palloshi, Altin ^c   Grigore, Liliana ^d   Garlaschelli, Katia ^d   Tramontana, Simona ^d   Tavano, Davide ^e   Airoldi, Flavio ^e   Manfredi, Angelo A ^a   Luigi Catapano, Alberico ^b,d,e   Danilo Norata, Giuseppe ^b,d  

^a VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

^c ISTITUTO CLINICO CITTÀ STUDI   (Italy)

^d Center for the Study of Atherosclerosis   (Italy)

^e IRCCS MULTIMEDICA   (Italy)

^f Azienda Ospedaliera della Provincia di Lodi   (Italy)

^g Heart Care Foundation   (Italy)

Author keywords

acute coronary syndrome; carotid artery intima media thickness; coronary artery disease; flow cytometry; regulatory T cells

Indexed keywords

CD4 ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR; MESSENGER RNA; TRANSCRIPTION FACTOR FOXP3; AUTACOID; BIOLOGICAL MARKER; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; IL10 PROTEIN, HUMAN; IL6 PROTEIN, HUMAN; INTERLEUKIN 6; INTERLEUKIN 7 RECEPTOR ALPHA;

ACUTE CORONARY SYNDROME; ACUTE HEART INFARCTION; ADULT; ARTERIAL WALL THICKNESS; ARTICLE; CAROTID ARTERY; COMMON CAROTID ARTERY; CONTROLLED STUDY; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY DISEASE; DISEASE MARKER; DISEASE SEVERITY; FEMALE; FLOW CYTOMETRY; GENE EXPRESSION; HUMAN; HUMAN CELL; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; ST SEGMENT ELEVATION; STABLE ANGINA PECTORIS; AGED; ANGINA PECTORIS; ANGIOCARDIOGRAPHY; BLOOD; CAROTID ARTERY DISEASE; CASE CONTROL STUDY; CD4 LYMPHOCYTE COUNT; ECHOGRAPHY; GENETICS; HOSPITALIZATION; IMMUNOLOGY; IMMUNOPHENOTYPING; MIDDLE AGED; PREDICTION AND FORECASTING; PROSPECTIVE STUDY; RADIOGRAPHY;

ACUTE CORONARY SYNDROME; AGED; ANGINA PECTORIS; BIOLOGICAL MARKERS; CAROTID ARTERY DISEASES; CASE-CONTROL STUDIES; CD4 LYMPHOCYTE COUNT; CORONARY ANGIOGRAPHY; CORONARY ARTERY DISEASE; FEMALE; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNOPHENOTYPING; INFLAMMATION MEDIATORS; INTERLEUKIN-10; INTERLEUKIN-6; INTERLEUKIN-7 RECEPTOR ALPHA SUBUNIT; MALE; MIDDLE AGED; PREDICTIVE VALUE OF TESTS; PROSPECTIVE STUDIES; RNA, MESSENGER; SEVERITY OF ILLNESS INDEX; T-LYMPHOCYTES, REGULATORY;

EID: 77955983228     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.110.206813     Document Type: Article

References (49)

1. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006;6:508-519.
2. Buffon A, Biasucci LM, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med. 2002;347:5-12.
3. Steppich BA, Moog P, Matissek C, Wisniowski N, Kuhle J, Joghetaei N, Neumann FJ, Schomig A, Ott I. Cytokine profiles and T cell function in acute coronary syndromes. Atherosclerosis. 2007;190:443-451.
4. Olofsson PS, Soderstrom LA, Wagsater D, Sheikine Y, Ocaya P, Lang F, Rabu C, Chen L, Rudling M, Aukrust P, Hedin U, Paulsson-Berne G, Sirsjo A, Hansson GK. CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation. 2008;117:1292-1301.
5. Mallat Z, Ait-Oufella H, Tedgui A. Regulatory T-cell immunity in atherosclerosis. Trends Cardiovasc Med. 2007;17:113-118.
6. Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12:178-180.
7. De Boer OJ, Van Der Meer JJ, Teeling P, Van Der Loos CM, Van Der Wal AC. Low numbers of FOXP3 positive regulatory T cells are present in all developmental stages of human atherosclerotic lesions. PLoS ONE. 2007; 2:e779.
8. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775-787.
9. Bacchetta R, Gambineri E, Roncarolo MG. Role of regulatory T cells and FOXP3 in human diseases. J Allergy Clin Immunol. 2007;120:227-235; quiz 236-1227
10. O'Garra A, Vieira P. Regulatory T cells and mechanisms of immune system control. Nat Med. 2004;10:801-805.
11. von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6:338-344.
12. Han SF, Liu P, Zhang W, Bu L, Shen M, Li H, Fan YH, Cheng K, Cheng HX, Li CX, Jia GL. The opposite-direction modulation of CD4 + CD25 + Tregs and T helper 1 cells in acute coronary syndromes. Clin Immunol. 2007;124:90-97.
13. Mor A, Luboshits G, Planer D, Keren G, George J. Altered status of CD4(+)CD25(+) regulatory T cells in patients with acute coronary syndromes. Eur Heart J. 2006;27:2530-2537.
14. Sardella G, De Luca L, Francavilla V, Accapezzato D, Mancone M, Sirinian MI, Fedele F, Paroli M. Frequency of naturally-occurring regulatory T cells is reduced in patients with ST-segment elevation myocardial infarction. Thromb Res. 2007;120:631-634.
15. Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, Yao R, Chen Y, Liao YH. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127:89-97.
16. Costantino CM, Baecher-Allan CM, Hafler DA. Human regulatory T cells and autoimmunity. Eur J Immunol. 2008;38:921-924.
17. Banham AH. Cell-surface IL-7 receptor expression facilitates the purification of FOXP3(+) regulatory T cells. Trends Immunol. 2006;27: 541-544.
18. Hoffmann HJ, Malling TM, Topcu A, Ryder LP, Nielsen KR, Varming K, Dahl R, Omland O, Sigsgaard T. CD4dimCD25bright Treg cell frequencies above a standardized gating threshold are similar in asthmatics and controls. Cytometry A. 2007;71:371-378.
19. Hartigan-O'Connor DJ, Poon C, Sinclair E, McCune JM. Human CD4 + regulatory T cells express lower levels of the IL-7 receptor a chain (CD127), allowing consistent identification and sorting of live cells. J Immunol Methods. 2007;319:41-52.
20. Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, Fazekas De St Groth B. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med. 2006;203:1693-1700.
21. Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas De St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4 + T reg cells. J Exp Med. 2006;203:1701-1711.
22. Kallikourdis M, Andersen KG, Welch KA, Betz AG. Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus. Proc Natl Acad Sci USA. 2007;104:594-599.
23. Wysocki CA, Jiang Q, Panoskaltsis-Mortari A, Taylor PA, McKinnon KP, Su L, Blazar BR, Serody JS. Critical role for CCR5 in the function of donor CD4 + CD25 + regulatory T cells during acute graft-versus-host disease. Blood. 2005;106:3300-3307.
24. Mor A, Planer D, Luboshits G, Afek A, Metzger S, Chajek-Shaul T, Keren G, George J. Role of naturally occurring CD4+ CD25+ regulatory T cells in experimental atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27:893-900.
25. Steffens S, Burger F, Pelli G, Dean Y, Elson G, Kosco-Vilbois M, Chatenoud L, Mach F. Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice. Circulation. 2006;114:1977-1984.
26. Groyer E, Nicoletti A, Ait-Oufella H, Khallou-Laschet J, Varthaman A, Gaston AT, Thaunat O, Kaveri SV, Blatny R, Stockinger H, Mallat Z, Caligiuri G. Atheroprotective effect of CD31 receptor globulin through enrichment of circulating regulatory T-cells. J Am Coll Cardiol. 2007; 50:344-350.
27. Sasaki N, Yamashita T, Takeda M, Shinohara M, Nakajima K, Tawa H, Usui T, Hirata K. Oral anti-CD3 antibody treatment induces regulatory T cells and inhibits the development of atherosclerosis in mice. Circulation. 2009;120:1996-2005.
28. Wigren M, Bengtsson D, Duner P, Olofsson K, Bjorkbacka H, Bengtsson E, Fredrikson GN, Nilsson J. Atheroprotective effects of Alum are associated with capture of oxidized LDL antigens and activation of regulatory T cells. Circ Res. 2009;104:e62-e70.
29. Norata GD, Raselli S, Grigore L, Garlaschelli K, Vianello D, Bertocco S, Zambon A, Catapano AL. Small dense LDL and VLDL predict common carotid artery IMT and elicit an inflammatory response in peripheral blood mononuclear and endothelial cells. Atherosclerosis. 2009;206: 556-562.
30. Stewart CC, Stewart SJ. Multiparameter analysis of leukocytes by flow cytometry. Methods Cell Biol. 1994;41:61-79.
31. Perfetto SP, Chattopadhyay PK, Roederer M. Seventeen-colour flow cytometry: unravelling the immune system. Nat Rev Immunol. 2004;4: 648-655.
32. Norata GD, Marchesi P, Pirillo A, Uboldi P, Chiesa G, Maina V, Garlanda C, Mantovani A, Catapano AL. Long pentraxin 3, a key component of innate immunity, is modulated by high-density lipoproteins in endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:925-931.
33. Yurchenko E, Tritt M, Hay V, Shevach EM, Belkaid Y, Piccirillo CA. CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence. J Exp Med. 2006;203:2451-2460.
34. Heller EA, Liu E, Tager AM, Yuan Q, Lin AY, Ahluwalia N, Jones K, Koehn SL, Lok VM, Aikawa E, Moore KJ, Luster AD, Gerszten RE. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation. 2006;113: 2301-2312.
35. Van Es T, Van Puijvelde GH, Foks AC, Habets KL, Bot I, Gilboa E, Van Berkel TJ, Kuiper J. Vaccination against Foxp3(+) regulatory T cells aggravates atherosclerosis. Atherosclerosis. 2010;209:74-80.
36. Patel S, Chung SH, White G, Bao S, Celermajer DS. The "atheroprotective" mediators apolipoproteinA-I and Foxp3 are over-abundant in unstable carotid plaques. [epub ahead of print May 28, 2009]. Int J Cardiol.
37. Platten M, Youssef S, Hur EM, Ho PP, Han MH, Lanz TV, Phillips LK, Goldstein MJ, Bhat R, Raine CS, Sobel RA, Steinman L. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1-and TH17-mediated autoimmunity. Proc Natl Acad Sci USA. 2009;106:14948- 14953.
38. Mausner-Fainberg K, Luboshits G, Mor A, Maysel-Auslender S, Rubinstein A, Keren G, George J. The effect of HMG-CoA reductase inhibitors on naturally occurring CD4 + CD25+ T cells. Atherosclerosis. 2008;197:829-839.
39. Finn AV, Kolodgie FD, Virmani R. Correlation between carotid intimal/medial thickness and atherosclerosis: a point of view from pathology. Arterioscler Thromb Vasc Biol. 2010;30:177-181.
40. Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010;30:182-185.
41. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group. N Engl J Med. 1999;340:14-22.
42. Van Puijvelde GH, Hauer AD, De Vos P, Van Den Heuvel R, Van Her-wijnen MJ, Van Der Zee R, Van Eden W, Van Berkel TJ, Kuiper J. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation. 2006;114:1968-1976.
43. Gotsman I, Sharpe AH, Lichtman AH. T-cell costimulation and coinhi-bition in atherosclerosis. Circ Res. 2008;103:1220-1231.
44. Zal B, Kaski JC, Arno G, Akiyu JP, Xu Q, Cole D, Whelan M, Russell N, Madrigal JA, Dodi IA, Baboonian C. Heat-shock protein 60-reactive CD4 + CD28null T cells in patients with acute coronary syndromes. Circulation. 2004;109:1230-1235.
45. Ammirati E, Vermi AC, Cianflone D, Banfi M, Foglieni C, Godino C, Airoldi F, Ferri LA, Gorman CL, Manfredi AA, Maseri A, Cope AP, Monaco C. Expansion of T-cell receptor zeta dim effector T cells in acute coronary syndromes. Arterioscler Thromb Vasc Biol. 2008;28: 2305-2311.
46. Hueman MT, Stojadinovic A, Storrer CE, Foley RJ, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Levels of circulating regulatory CD4 + CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine. Breast Cancer Res Treat. 2006;98:17-29.
47. Bour-Jordan H, Salomon BL, Thompson HL, Szot GL, Bernhard MR, Bluestone JA. Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells. J Clin Invest. 2004;114: 979-987.
48. Hosono M, De Boer OJ, Van Der Wal AC, Van Der Loos CM, Teeling P, Piek JJ, Ueda M, Becker AE. Increased expression of T cell activation markers (CD25, CD26, CD40L and CD69) in atherectomy specimens of patients with unstable angina and acute myocardial infarction. Atherosclerosis. 2003;168:73-80.
49. Mottonen M, Heikkinen J, Mustonen L, Isomaki P, Luukkainen R, Lassila O. CD4+ CD25+ T cells with the phenotypic and functional characteristics of regulatory T cells are enriched in the synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 2005;140:360-367.