(Circulation. 2000;102:1114.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Evidence for Antigen-Driven T-Cell Response in Unstable Angina
From the Center for Molecular Medicine (G.C., G.P., A.N., G.K.H.), Karolinska Institute, Stockholm, Sweden; INSERM U460 (G.C.), Hôpital Bichat, and INSERM U430 (A.N.), Hôpital Broussais, Paris, France; and the Cardiology Institute (A.M.), Catholic University, Rome, Italy.
Correspondence to Dr Giuseppina Caligiuri, INSERM U460, Hôpital Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France. E-mail caligiu{at}bichat.inserm.fr
Background—Activation of T cells and macrophages has been associated with unstable angina (UA), but whether this reflects specific immune responses remains unclear.
Methods and Results—We analyzed the repertoire and the length of complementarity-determining region 3 of the T-cell receptor (TCR) ß-chain variable (BV) gene segments of activated lymphocytes in 23 patients with UA, 13 patients with chronic stable angina (CSA), and 6 normal control subjects. We also tested the proliferation of systemic T cells in response to autologous coronary plaque proteins, oxidized LDL, and Chlamydia pneumoniae as candidate antigens, in vitro. The activated T cell–TCRBV repertoire was perturbed in 13 (57%) of 23 UA patients versus 3 (23%) of 13 CSA patients (P=0.016) and was restricted to 6 (28%) of 21 expanded TCRBV families; all were significantly higher in UA than in CSA patients. At least one monotypic or oligotypic activated TCRBV population was found in 15 (65%) of 23 UA patients and in 3 (23%) of 13 CSA patients (P<0.001). Finally, T cells from UA patients, but not from CSA patients or normal control subjects, proliferated in response to autologous proteins from coronary culprit lesions and/or to oxidized LDL.
Conclusions—Our findings suggest that the T-cell response observed in UA patients is antigen-driven and directed to antigens contained in the culprit coronary atherosclerotic plaques.
Key Words: angina • ischemia • prognosis • lymphocytes • antigens
This article has been cited by other articles:
 |
|
 |
|
  E. Ammirati, A.-C. Vermi, D. Cianflone, M. Banfi, C. Foglieni, C. Godino, F. Airoldi, L. A. Ferri, C. L. Gorman, A. A. Manfredi, et al. Expansion of T-Cell Receptor {zeta}dim Effector T Cells in Acute Coronary Syndromes Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2305 - 2311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Liuzzo, L. M. Biasucci, G. Trotta, S. Brugaletta, M. Pinnelli, G. Digianuario, V. Rizzello, A. G. Rebuzzi, C. Rumi, A. Maseri, et al. Unusual CD4+CD28null T Lymphocytes and Recurrence of Acute Coronary Events J. Am. Coll. Cardiol., October 9, 2007; 50(15): 1450 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Groyer, A. Nicoletti, H. Ait-Oufella, J. Khallou-Laschet, A. Varthaman, A.-T. Gaston, O. Thaunat, S. V. Kaveri, R. Blatny, H. Stockinger, et al. Atheroprotective Effect of CD31 Receptor Globulin Through Enrichment of Circulating Regulatory T-Cells J. Am. Coll. Cardiol., July 24, 2007; 50(4): 344 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Wu, M. S. Maurer, R. A. Friedman, C. C. Marboe, E. M. Ruiz-Vazquez, R. Ramakrishnan, A. Schwartz, M. D. Tilson, A. S. Stewart, and R. Winchester The Lymphocytic Infiltration in Calcific Aortic Stenosis Predominantly Consists of Clonally Expanded T Cells J. Immunol., April 15, 2007; 178(8): 5329 - 5339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ranjbaran, S. I. Sokol, A. Gallo, R. E. Eid, A. O. Iakimov, A. D'Alessio, J. R. Kapoor, S. Akhtar, C. J. Howes, M. Aslan, et al. An Inflammatory Pathway of IFN-{gamma} Production in Coronary Atherosclerosis J. Immunol., January 1, 2007; 178(1): 592 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Caligiuri and A. Nicoletti Lymphocyte responses in acute coronary syndromes: lack of regulation spawns deviant behaviour Eur. Heart J., November 1, 2006; 27(21): 2485 - 2486. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. De Palma, F. Del Galdo, G. Abbate, M. Chiariello, R. Calabro, L. Forte, G. Cimmino, M. F. Papa, M. G. Russo, G. Ambrosio, et al. Patients With Acute Coronary Syndrome Show Oligoclonal T-Cell Recruitment Within Unstable Plaque: Evidence for a Local, Intracoronary Immunologic Mechanism Circulation, February 7, 2006; 113(5): 640 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Khallou-Laschet, G. Caligiuri, E. Groyer, E. Tupin, A.-T. Gaston, B. Poirier, M. Kronenberg, J. L. Cohen, D. Klatzmann, S. V. Kaveri, et al. The Proatherogenic Role of T Cells Requires Cell Division and Is Dependent on the Stage of the Disease Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 353 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S G Baidya and Q-T Zeng Helper T cells and atherosclerosis: the cytokine web Postgrad. Med. J., December 1, 2005; 81(962): 746 - 752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G Liuzzo, G Giubilato, and M Pinnelli T cells and cytokines in atherogenesis Lupus, September 1, 2005; 14(9): 732 - 735. [Abstract] [PDF]
|
|
|
|
|
|
G. Caligiuri, E. Groyer, J. Khallou-Laschet, A. A. H. Zen, J. Sainz, D. Urbain, A.-T. Gaston, M. Lemitre, A. Nicoletti, and A. Lafont Reduced Immunoregulatory CD31+ T Cells in the Blood of Atherosclerotic Mice With Plaque Thrombosis Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1659 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. K. Hansson Inflammation, Atherosclerosis, and Coronary Artery Disease N. Engl. J. Med., April 21, 2005; 352(16): 1685 - 1695. [Full Text] [PDF]
|
|
|
|
|
|
C. Monaco, E. Rossi, D. Milazzo, F. Citterio, F. Ginnetti, G. D'Onofrio, D. Cianflone, F. Crea, L. M. Biasucci, and A. Maseri Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden J. Am. Coll. Cardiol., January 18, 2005; 45(2): 238 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Legan, O. Vraspir-Porenta, D. Kese, R. Zorc-Pleskovic, and M. Zorc Histopathologic Signs for the Inflammatory Role of Chlamydia pneumoniae in the High-Grade Atherosclerotic Coronary Artery Wall Angiology, September 1, 2004; 55(5): 525 - 531. [Abstract] [PDF]
|
|
|
|
|
|
A. Abbate, E. Bonanno, A. Mauriello, R. Bussani, G. G.L. Biondi-Zoccai, G. Liuzzo, A. M. Leone, F. Silvestri, A. Dobrina, F. Baldi, et al. Widespread Myocardial Inflammation and Infarct-Related Artery Patency Circulation, July 6, 2004; 110(1): 46 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-J. Priebe Triggers of perioperative myocardial ischaemia and infarction Br. J. Anaesth., July 1, 2004; 93(1): 9 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Zal, J. C. Kaski, G. Arno, J. P. Akiyu, Q. Xu, D. Cole, M. Whelan, N. Russell, J. A. Madrigal, I. A. Dodi, et al. Heat-Shock Protein 60-Reactive CD4+CD28null T Cells in Patients With Acute Coronary Syndromes Circulation, March 16, 2004; 109(10): 1230 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-P. Yang, L.-J. Ho, Y.-L. Lin, S.-M. Cheng, T.-P. Tsao, D.-M. Chang, Y.-L. Hsu, C.-Y. Shih, T.-Y. Juan, and J.-H. Lai Carvedilol, a new antioxidative {beta}-blocker, blocks in vitro human peripheral blood T cell activation by downregulating NF-{kappa}B activity Cardiovasc Res, September 1, 2003; 59(3): 776 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Dechend, J. Gieffers, R. Dietz, A. Joerres, J. Rupp, F. C. Luft, and M. Maass Hydroxymethylglutaryl Coenzyme A Reductase Inhibition Reduces Chlamydia pneumoniae-Induced Cell Interaction and Activation Circulation, July 22, 2003; 108(3): 261 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. G. Neri Serneri, M. Boddi, P. A. Modesti, I. Cecioni, M. Coppo, M. L. Papa, T. Toscano, A. Marullo, and M. Chiavarelli Immunomediated and Ischemia-Independent Inflammation of Coronary Microvessels in Unstable Angina Circ. Res., June 27, 2003; 92(12): 1359 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Casscells, M. Naghavi, and J. T. Willerson Vulnerable Atherosclerotic Plaque: A Multifocal Disease Circulation, April 29, 2003; 107(16): 2072 - 2075. [Full Text] [PDF]
|
|
|
|
|
|
L. G. Spagnoli, E. Bonanno, A. Mauriello, G. Palmieri, A. Partenzi, G. Sangiorgi, and F. Crea Multicentric inflammation in epicardial coronary arteries of patients dying of acute myocardial infarction J. Am. Coll. Cardiol., November 6, 2002; 40(9): 1579 - 1588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kharbanda, B. Walton, M. Allen, N. Klein, A. D. Hingorani, R. J. MacAllister, and P. Vallance Prevention of Inflammation-Induced Endothelial Dysfunction: A Novel Vasculo-Protective Action of Aspirin Circulation, June 4, 2002; 105(22): 2600 - 2604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stollberger and J. Finsterer Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis Clin. Vaccine Immunol., March 1, 2002; 9(2): 207 - 215. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Maseri and D. Cianflone Inflammation in acute coronary syndromes Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B8 - B13. [Abstract] [PDF]
|
|
|
|
|
|
A. Ciervo, P. Visca, A. Petrucca, L. M. Biasucci, A. Maseri, and A. Cassone Antibodies to 60-Kilodalton Heat Shock Protein and Outer Membrane Protein 2 of Chlamydia pneumoniae in Patients with Coronary Heart Disease Clin. Vaccine Immunol., January 1, 2002; 9(1): 66 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.F. Bentzon and E. Falk Coronary plaques calling for action -- why, where and how many? Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I3 - I9. [Abstract] [PDF]
|
|
|
|
|
|
X. Zhou, A. Nicoletti, R. Elhage, and G. K. Hansson Transfer of CD4+ T Cells Aggravates Atherosclerosis in Immunodeficient Apolipoprotein E Knockout Mice Circulation, December 12, 2000; 102(24): 2919 - 2922. [Abstract] [Full Text] [PDF]
|
|