Adaptive immunity in atherogenesis: New insights and therapeutic approaches

Journal of Clinical Investigation

Volumn 123, Issue 1, 2013, Pages 27-36

  Lichtman, Andrew H ^a   Binder, Christoph J ^b,c,d   Tsimikas, Sotirios ^b   Witztum, Joseph L ^b  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c MEDICAL UNIVERSITY OF VIENNA   (Austria)

^d ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; ATHEROGENESIS; ATHEROSCLEROSIS; B LYMPHOCYTE; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; INTROSPECTION; LYMPHOCYTE PROLIFERATION; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE; TH1 CELL; TH17 CELL;

ADAPTIVE IMMUNITY; ANIMALS; ATHEROSCLEROSIS; HUMANS; INFLAMMATION; LIPOPROTEINS, LDL; OXIDATION-REDUCTION;

EID: 84873825492     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI63108     Document Type: Review

References (158)

1. Steinberg D, Witztum JL. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30(12): 2311-2316.
2. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3): 341-355.
3. Packard RR, Lichtman AH, Libby P. Innate and adaptive immunity in atherosclerosis. Semin Immunopathol. 2009;31(1): 5-22.
4. Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011; 17(11): 1410-1422.
5. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3): 204-212.
6. Libby P. Counterregulation rules in atherothrombosis. J Am Coll Cardiol. 2012;59(16): 1438-1440.
7. Miller YI, et al. Oxidation-specific epitopes are danger- associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ Res. 2011;108(2): 235-248.
8. Rosenfeld ME, Campbell LA. Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thromb Haemost. 2011;106(5): 858-867.
9. Tufano A, et al. The infectious burden in atherothrombosis. Semin Thromb Hemost. 2012;38(5): 515-523.
10. Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol. 2004;22: 361-403.
11. Duewell P, et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature. 2010;464(7293): 1357-1361.
12. Chang MK, et al. Apoptotic cells with oxidation- specific epitopes are immunogenic and proinflammatory. J Exp Med. 2004;200(11): 1359-1370.
13. Mallat Z, Taleb S, Ait-Oufella H, Tedgui A. The role of adaptive T cell immunity in atherosclerosis. J Lipid Res. 2009;50(suppl):S364-S369.
14. Palinski W, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Natl Acad Sci U S A. 1989;86(4): 1372-1376.
15. Ylä-Herttuala S, Palinski W, Butler SW, Picard S, Steinberg D, Witztum JL. Rabbit and human atherosclerotic lesions contain IgG that recognizes epitopes of oxidized LDL. Arterioscler Thromb. 1994;14(1): 32-40.
16. Wade NS, Major AS. The problem of accelerated atherosclerosis in systemic lupus erythematosus: insights into a complex co-morbidity. Thromb Haemost. 2011;106(5): 849-857.
17. Kitas GD, Gabriel SE. Cardiovascular disease in rheumatoid arthritis: state of the art and future perspectives. Ann Rheum Dis. 2011;70(1): 8-14.
18. Patel RV, Shelling ML, Prodanovich S, Federman DG, Kirsner RS. Psoriasis and vascular disease-risk factors and outcomes: a systematic review of the literature. J Gen Intern Med. 2011;26(9): 1036-1049.
19. Dansky HM, Charlton SA, Harper MM, Smith JD. T and B lymphocytes play a minor role in atherosclerotic plaque formation in the apolipoprotein E-deficient mouse. Proc Natl Acad Sci U S A. 1997; 94(9): 4642-4646.
20. Daugherty A. The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E-/- mice. J Clin Invest. 1997; 100(6): 1575-1580.
21. Zhou X, Nicoletti A, Elhage R, Hansson GK. Transfer of CD4+ T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation. 2000;102(24): 2919-2922.
22. Song L, Leung C, Schindler C. Lymphocytes are important in early atherosclerosis. J Clin Invest. 2001;108(2): 251-259.
23. Reardon CA, et al. Effect of immune deficiency on lipoproteins and atherosclerosis in male apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21(6): 1011-1016.
24. Jonasson L, Holm J, Skalli O, Bondjers G, Hansson GK. Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986; 6(2): 131-138.
25. Stemme S, Faber B, Holm J, Wiklund O, Witztum JL, Hansson GK. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A. 1995; 92(9): 3893-3897.
26. Hermansson A, et al. Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis. J Exp Med. 2010;207(5): 1081-1093.
27. Ketelhuth DF, Hansson GK. Cellular immunity, low-density lipoprotein and atherosclerosis: break of tolerance in the artery wall. Thromb Haemost. 2011;106(5): 779-786.
28. Getz GS, Vanderlaan PA, Reardon CA. Natural killer T cells in lipoprotein metabolism and atherosclerosis. Thromb Haemost. 2011;106(5): 814-819.
29. Betjes MG, Meijers RW, de Wit LE, Litjens NH. A killer on the road: circulating CD4(+)CD28null T cells as cardiovascular risk factor in ESRD patients. J Nephrol. 2012;25(2): 183-191.
30. Olofsson PS. Targeting T cell costimulation to prevent atherothrombosis. Circ Res. 2012;110(6): 800-801.
31. Buono C, Come CE, Stavrakis G, Maguire GF, Connelly PW, Lichtman AH. Influence of interferon- gamma on the extent and phenotype of diet-induced atherosclerosis in the LDLR-deficient mouse. Arterioscler Thromb Vasc Biol. 2003;23(3): 454-460.
32. Gupta S, Pablo AM, Jiang X, Wang N, Tall AR, Schindler C. IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997; 99(11): 2752-2761.
33. Buono C, Binder CJ, Stavrakis G, Witztum JL, Glimcher LH, Lichtman AH. T-bet deficiency reduces atherosclerosis and alters plaque antigen- specific immune responses. Proc Natl Acad Sci U S A. 2005;102(5): 1596-1601.
34. Whitman SC, Ravisankar P, Elam H, Daugherty A. Exogenous interferon-[gamma] enhances atherosclerosis in apolipoprotein E-/- mice. Am J Pathol. 2000;157(6): 1819-1824.
35. Ait-Oufella H, Taleb S, Mallat Z, Tedgui A. Recent advances on the role of cytokines in atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(5): 969-979.
36. Davenport P, Tipping PG. The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol. 2003;163(3): 1117-1125.
37. Whitman SC, Ravisankar P, Daugherty A. Interleukin- 18 enhances atherosclerosis in apolipoprotein E(-/-) mice through release of interferon-gamma. Circ Res. 2002;90(2):E34-E38.
38. Ryan C, et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA. 2011;306(8): 864-871.
39. Tzellos T, Kyrgidis A, Zouboulis CC. Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials [published online ahead of print March 8, 2012]. J Eur Acad Dermatol Venereol. doi:10.1111/j.1468-3083.2012.04500.x.
40. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27: 485-517.
41. Taleb S, Tedgui A, Mallat Z. Interleukin-17: friend or foe in atherosclerosis? Curr Opin Lipidol. 2010;21(5): 404-408.
42. de Boer OJ, et al. Differential expression of interleukin- 17 family cytokines in intact and complicated human atherosclerotic plaques. J Pathol. 2010;220(4): 499-508.
43. Taleb S, et al. Loss of SOCS3 expression in T cells reveals a regulatory role for interleukin-17 in atherosclerosis. J Exp Med. 2009;206(10): 2067-2077.
44. Eid RE, et al. Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation. 2009;119(10): 1424-1432.
45. Zhang X, et al. Interleukin-17A gene variants and risk of coronary artery disease: a large angiography-based study. Clin Chim Acta. 2011;412(3-4): 327-331.
46. Wang Z, et al. Increased Th17 cells in coronary artery disease are associated with neutrophilic inflammation. Scand Cardiovasc J. 2011;45(1): 54-61.
47. Hashmi S, Zeng QT. Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease. Coron Artery Dis. 2006;17(8): 699-706.
48. Cheng X, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127(1): 89-97.
49. Zhao Z, et al. Activation of Th17/Th1 and Th1, but not Th17, is associated with the acute cardiac event in patients with acute coronary syndrome. Atherosclerosis. 2011;217(2): 518-524.
50. Patel KD, et al. Interleukin 17: an unlikely marker of acute coronary syndrome? Atherosclerosis. 2009; 205(1): 33-34.
51. Erbel C. Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice. J Immunol. 2009;183(12): 8167-8175.
52. Gao Q, et al. A critical function of Th17 proinflammatory cells in the development of atherosclerotic plaque in mice. J Immunol. 2010;185(10): 5820-5827.
53. Usui F, et al. Interleukin-17 deficiency reduced vascular inflammation and development of atherosclerosis in Western diet-induced apoE-deficient mice. Biochem Biophys Res Commun. 2012;420(1): 72-77.
54. Butcher MJ, Gjurich BN, Phillips T, Galkina EV. The IL-17A/IL-17RA axis plays a proatherogenic role via the regulation of aortic myeloid cell recruitment. Circ Res. 2012;110(5): 675-687.
55. van Es T. Attenuated atherosclerosis upon IL-17R signaling disruption in LDLr deficient mice. Biochem Biophys Res Commun. 2009;388(2): 261-265.
56. Chen S, Shimada K, Zhang W, Huang G, Crother TR, Arditi M. IL-17A is proatherogenic in high-fat diet-induced and chlamydia pneumoniae infection- accelerated atherosclerosis in mice. J Immunol. 2010;185(9): 5619-5627.
57. Danzaki K, et al. Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32(2): 273-280.
58. Cheng X, et al. Inhibition of IL-17A in atherosclerosis. Atherosclerosis. 2011;215(2): 471-474.
59. Madhur MS, et al. Role of interleukin 17 in Inflammation, atherosclerosis, and vascular function in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2011;31(7): 1565-1572.
60. Ait-Oufella H, et al. B cell depletion reduces the development of atherosclerosis in mice. J Exp Med. 2010;207(8): 1579-1587.
61. Wilke CM, Bishop K, Fox D, Zou W. Deciphering the role of Th17 cells in human disease. Trends Immunol. 2011;32(12): 603-611.
62. Eid RE, et al. Interleukin-17 and interferon-[gamma] are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation. 2009;119(10): 1424-1432.
63. Lee YK, et al. Late developmental plasticity in the T helper 17 lineage. Immunity. 2009;30(1): 92-107.
64. Leonardi C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366(13): 1190-1199.
65. Papp KA, et al. Brodalumab, an anti-interleukin- 17-receptor antibody for psoriasis. N Engl J Med. 2012;366(13): 1181-1189.
66. Waisman A. To be 17 again - anti-interleukin-17 treatment for psoriasis. N Engl J Med. 2012; 366(13): 1251-1252.
67. Zhou X, Paulsson G, Stemme S, Hansson GK. Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice. J Clin Invest. 1998;101(8): 1717-1725.
68. King VL, Szilvassy SJ, Daugherty A. Interleukin-4 deficiency decreases atherosclerotic lesion formation in a site-specific manner in female LDL receptor-/- mice. Arterioscler Thromb Vasc Biol. 2002;22(3): 456-461.
69. King VL, Cassis LA, Daugherty A. Interleukin-4 does not influence development of hypercholesterolemia or angiotensin II-induced atherosclerotic lesions in mice. Am J Pathol. 2007;171(6): 2040-2047.
70. Cardilo-Reis L, et al. Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med. 2012;4(10): 1072-1086.
71. Binder CJ, et al. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest. 2004;114(3): 427-437.
72. Corren J. Inhibition of interleukin-5 for the treatment of eosinophilic diseases. Discov Med. 2012; 13(71): 305-312.
73. Kleindienst R, Xu Q, Willeit J, Waldenberger FR, Weimann S, Wick G. Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. Am J Pathol. 1993;142(6): 1927-1937.
74. van der Wal AC, Das PK, Bentz van de Berg D, van der Loos CM, Becker AE. Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. Lab Invest. 1989;61(2): 166-170.
75. Bu DX, et al. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5): 1100-1107.
76. Kolbus D, et al. CD8+ T cell activation predominate early immune responses to hypercholesterolemia in Apoe-/- mice. BMC Immunol. 2010;11:58.
77. Elhage R, et al. Deleting TCR alpha beta+ or CD4+ T lymphocytes leads to opposite effects on site-specific atherosclerosis in female apolipoprotein E-deficient mice. Am J Pathol. 2004;165(6): 2013-2018.
78. Kolbus D, et al. TAP1-deficiency does not alter atherosclerosis development in Apoe?/? mice. PLoS One. 2012;7(3):e33932.
79. Binder CJ, et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med. 2003;9(6): 736-743.
80. Sun J, et al. Deficiency of antigen-presenting cell invariant chain reduces atherosclerosis in mice. Circulation. 2010;122(8): 808-820.
81. Lewis MJ, Malik TH, Ehrenstein MR, Boyle JJ, Botto M, Haskard DO. Immunoglobulin M is required for protection against atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 2009;120(5): 417-426.
82. Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis car ried by B cells of hypercholesterolemic mice. J Clin Invest. 2002;109(6): 745-753.
83. Kyaw T, et al. B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res. 2011;109(8): 830-840.
84. Ravandi A, et al. Relationship of IgG and IgM autoantibodies and immune complexes to oxidized LDL with markers of oxidation and inflammation and cardiovascular events: results from the EPIC-Norfolk Study. J Lipid Res. 2011;52(10): 1829-1836.
85. Griffin DO, Holodick NE, Rothstein TL. Human B1 cells in umbilical cord and adult peripheral blood express the novel phenotype CD20+ CD27+ CD43+ CD70. J Exp Med. 2011;208(1): 67-80.
86. Binder CJ, et al. Innate and acquired immunity in atherogenesis. Nat Med. 2002;8(11): 1218-1226.
87. Gounopoulos P, Merki E, Hansen LF, Choi SH, Tsimikas S. Antibodies to oxidized low density lipoprotein: epidemiological studies and potential clinical applications in cardiovascular disease. Minerva Cardioangiol. 2007;55(6): 821-837.
88. Tsimikas S, Palinski W, Witztum JL. Circulating autoantibodies to oxidized LDL correlate with arterial accumulation and depletion of oxidized LDL in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21(1): 95-100.
89. Palinski W, Miller E, Witztum JL. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis. Proc Natl Acad Sci U S A. 1995;92(3): 821-825.
90. Hansson GK, Nilsson J. Vaccination against atherosclerosis? Induction of atheroprotective immunity. Semin Immunopathol. 2009;31(1): 95-101.
91. Nilsson J, Björkbacka H, Fredrikson GN. Apolipoprotein B100 autoimmunity and atherosclerosis - disease mechanisms and therapeutic potential. Curr Opin Lipidol. 2012;23(5): 422-428.
92. Tsimikas S, et al. Human oxidation-specific antibodies reduce foam cell formation and atherosclerosis progression. J Am Coll Cardiol. 2011; 58(16): 1715-1727.
93. Major AS, Fazio S, Linton MF. B-lymphocyte deficiency increases atherosclerosis in LDL receptor- null mice. Arterioscler Thromb Vasc Biol. 2002; 22(11): 1892-1898.
94. Kyaw T, et al. Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. J Immunol. 2010;185(7): 4410-4419.
95. Kyaw T, et al. Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE mice attenuates atherosclerosis by potently ameliorating arterial inflammation. PLoS One. 2012;7(1):e29371.
96. Sage AP, et al. BAFF receptor deficiency reduces the development of atherosclerosis in mice - brief report. Arterioscler Thromb Vasc Biol. 2012;32(7): 1573-1576.
97. Doran AC, et al. B-cell aortic homing and atheroprotection depend on Id3. Circ Res. 2012;110(1):e1-e12.
98. Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol. 2012;30: 221-241.
99. Griffin DO, Rothstein TL. Human "orchestrator" CD11b(+) B1 cells spontaneously secrete IL-10 and regulate T cell activity. Mol Med. 2012; 18(9): 1003-1008.
100. Kelly JA, et al. Inhibition of arterial lesion progression in CD16-deficient mice: evidence for altered immunity and the role of IL-10. Cardiovasc Res. 2010; 85(1): 224-231.
101. Hernandez-Vargas P, et al. Fcgamma receptor deficiency confers protection against atherosclerosis in apolipoprotein E knockout mice. Circ Res. 2006;99(11): 1188-1196.
102. Zhao M, et al. FcgammaRIIB inhibits the development of atherosclerosis in low-density lipoprotein receptor-deficient mice. J Immunol. 2010; 184(5): 2253-2260.
103. Mendez-Fernandez YV, et al. The inhibitory FcgammaRIIb modulates the inflammatory response and influences atherosclerosis in male apoE(-/-) mice. Atherosclerosis. 2011;214(1): 73-80.
104. Wang J, et al. IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice. J Clin Invest. 2011;121(9): 3564-3577.
105. Speidl WS, Kastl SP, Huber K, Wojta J. Complement in atherosclerosis: friend or foe? J Thromb Haemost. 2011;9(3): 428-440.
106. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30: 531-564.
107. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8(12): 1353-1362.
108. Wing K, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322(5899): 271-275.
109. Qureshi OS, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332(6029): 600-603.
110. von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6(4): 338-344.
111. Gotsman I, et al. Impaired regulatory T-cell response and enhanced atherosclerosis in the absence of inducible costimulatory molecule. Circulation. 2006;114(19): 2047-2055.
112. Maganto-Garcia E, Tarrio ML, Grabie N, Bu DX, Lichtman AH. Dynamic changes in regulatory T cells are linked to levels of diet-induced hypercholesterolemia. Circulation. 2011;124(2): 185-195.
113. Ng HP, Burris RL, Nagarajan S. Attenuated atherosclerotic lesions in apoE-Fc?-chain-deficient hyperlipidemic mouse model is associated with inhibition of Th17 cells and promotion of regulatory T cells. J Immunol. 2011;187(11): 6082-6093.
114. Engel D, et al. Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response. FASEB J. 2011;25(11): 3838-3848.
115. Weber C, et al. CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice. J Clin Invest. 2011; 121(7): 2898-2910.
116. Taleb S, et al. Defective leptin/leptin receptor signaling improves regulatory T cell immune response and protects mice from atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(12): 2691-2698.
117. 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(8):e779.
118. Patel S, Chung SH, White G, Bao S, Celermajer DS. The "atheroprotective" mediators apolipoproteinA- I and Foxp3 are over-abundant in unstable carotid plaques. Int J Cardiol. 2010;145(2): 183-187.
119. Kofler S, Sisic Z, Shvets N, Lohse P, Weis M. Expression of circulatory dendritic cells and regulatory T-cells in patients with different subsets of coronary artery disease. J Cardiovasc Pharmacol. 2011; 57(5): 542-549.
120. Potekhina AV, et al. CD4(+)CD25(high)CD127(low) regulatory T cells in patients with stable angina and their dynamics after intracoronary sirolimus-eluting stent implantation. Hum Immunol. 2011; 72(7): 553-557.
121. Meng X, et al. Statins induce the accumulation of regulatory T cells in atherosclerotic plaque. Mol Med. 2012;18(1): 598-605.
122. Zhang D, et al. Effect of oral atorvastatin on CD4+CD25+ regulatory T cells, FoxP3 expression, and prognosis in patients with ST-segment elevated myocardial infarction before primary percutaneous coronary intervention. J Cardiovasc Pharmacol. 2011;57(5): 536-541.
123. Mausner-Fainberg K, et al. The effect of HMGCoA reductase inhibitors on naturally occurring CD4+CD25+ T cells. Atherosclerosis. 2008; 197(2): 829-839.
124. Bu DX, Griffin G, Lichtman AH. Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol. 2011;22(3): 165-170.
125. Itano AA, Jenkins MK. Antigen presentation to naive CD4 T cells in the lymph node. Nat Immunol. 2003;4(8): 733-739.
126. Paulson KE, Zhu S-N, Chen M, Nurmohamed S, Jongstra-Bilen J, Cybulsky MI. Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res. 2010; 106(2): 383-390.
127. Ma-Krupa W, Jeon M-S, Spoerl S, Tedder TF, Goronzy JJ, Weyand CM. Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J Exp Med. 2004;199(2): 173-183.
128. Koltsova EK, Ley K. How dendritic cells shape atherosclerosis. Trends Immunol. 2011;32(11): 540-547.
129. Butcher MJ, Galkina EV. Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets in the healthy and atherosclerosis- prone aorta. Front Physiol. 2012;3:44.
130. Packard RR, Maganto-Garcia E, Gotsman I, Tabas I, Libby P, Lichtman AH. CD11c(+) dendritic cells maintain antigen processing, presentation capabilities, and CD4(+) T-cell priming efficacy under hypercholesterolemic conditions associated with atherosclerosis. Circ Res. 2008;103(9): 965-973.
131. Koltsova EK, et al. Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis. J Clin Invest. 2012;122(9): 3114-3126.
132. Doring Y, et al. Auto-antigenic protein-DNA complexes stimulate plasmacytoid dendritic cells to promote atherosclerosis. Circulation. 2012; 125(13): 1673-1683.
133. Lichtman AH. T cell costimulatory and coinhibitory pathways in vascular inflammatory diseases. Front Physiol. 2012;3:18.
134. de Boer OJ, Hirsch F, van der Wal AC, van der Loos CM, Das PK, Becker AE. Costimulatory molecules in human atherosclerotic plaques: an indication of antigen specific T lymphocyte activation. Atherosclerosis. 1997;133(2): 227-234.
135. Afek A, Harats D, Roth A, Keren G, George J. A functional role for inducible costimulator (ICOS) in atherosclerosis. Atherosclerosis. 2005;183(1): 57-63.
136. Buono C, Pang H, Uchida Y, Libby P, Sharpe AH, Lichtman AH. B7-1/B7-2 costimulation regulates plaque antigen-specific T-cell responses and atherogenesis in low-density lipoprotein receptor-deficient mice. Circulation. 2004;109(16): 2009-2015.
137. Wang X, et al. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet. 2005; 37(4): 365-372.
138. Olofsson PS, et al. CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice. Circulation. 2008;117(10): 1292-1301.
139. van Wanrooij EJ, van Puijvelde GH, de Vos P, Yagita H, van Berkel TJ, Kuiper J. Interruption of the Tnfrsf4/Tnfsf4 (OX40/OX40L) pathway attenuates atherogenesis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2007;27(1): 204-210.
140. Jeon HJ, et al. CD137 (4-1BB) deficiency reduces atherosclerosis in hyperlipidemic mice. Circulation. 2010;121(9): 1124-1133.
141. Dumitriu IE, et al. High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD- 28null T cells in patients with acute coronary syndrome. Circ Res. 2012;110(6): 857-869.
142. Gotsman I, Grabie N, Dacosta R, Sukhova G, Sharpe A, Lichtman AH. Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice. J Clin Invest. 2007;117(10): 2974-2982.
143. Lee J, et al. Contributions of PD-1/PD-L1 pathway to interactions of myeloid DCs with T cells in atherosclerosis. J Mol Cell Cardiol. 2009;46(2): 169-176.
144. 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(7): 979-987.
145. Ait-Oufella H, et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med. 2006;12(2): 178-180.
146. Maron R, et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aortic arch of low-density lipoprotein receptor-deficient mice. Circulation. 2002; 106(13): 1708-1715.
147. van Puijvelde GH, et al. Induction of oral tolerance to HSP60 or an HSP60-peptide activates T cell regulation and reduces atherosclerosis. Arterioscler Thromb Vasc Biol. 2007;27(12): 2677-2683.
148. Zhong Y, et al. CD4+LAP+ and CD4+CD25 +Foxp3+ regulatory T cells induced by nasal oxidized low-density lipoprotein suppress effector T cells response and attenuate atherosclerosis in ApoE-/- mice. J Clin Immunol. 2012;32(5): 1104-1117.
149. van Puijvelde GH, et al. Induction of oral tolerance to oxidized low-density lipoprotein ameliorates atherosclerosis. Circulation. 2006;114(18): 1968-1976.
150. George J, et al. Suppression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with beta 2-glycoprotein I. Cardiovasc Res. 2004;62(3): 603-609.
151. Hermansson A, Johansson DK, Ketelhuth DF, Andersson J, Zhou X, Hansson GK. Immunotherapy with tolerogenic apolipoprotein B-100-loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice. Circulation. 2011;123(10): 1083-1091.
152. Herbin O, et al. Regulatory T-cell response to apolipoprotein B100-derived peptides reduces the development and progression of atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2012;32(3): 605-612.
153. Topalian SL, Weiner GJ, Pardoll DM. Cancer immunotherapy comes of age. J Clin Oncol. 2011; 29(36): 4828-4836.
154. Taleb A, Witztum JL, Tsimikas S. Oxidized phospholipids on apoB-100-containing lipoproteins: a biomarker predicting cardiovascular disease and cardiovascular events. Biomark Med. 2011;5(5): 673-694.
155. Kiechl S, et al. Oxidized phospholipids, lipoprotein (a), lipoprotein-associated phospholipase A2 activity, and 10-year cardiovascular outcomes: prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol. 2007;27(8): 1788-1795.
156. Briley-Saebo KC, et al. In vivo detection of oxidation- specific epitopes in atherosclerotic lesions using biocompatible manganese molecular magnetic imaging probes. J Am Coll Cardiol. 2012; 59(6): 616-626.
157. Ridker P, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: A Phase IIb Randomized, Placebo-Controlled Trial. Circulation. 2012;126(23): 2739-2748.
158. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1 inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162(4): 597-605.