Perturbation of the T-cell repertoire in patients with unstable angina.
Abstract
Background —Monocytes are constitutively activated in unstable angina (UA), resulting in the production of IL-6 and the upregulation of acute phase proteins. Underlying mechanisms are not understood. To explore whether the production of the potent monocyte activator IFN-γ is altered in UA, we compared cytokine production by T lymphocytes in patients with UA (Braunwald’s class IIIB) and with stable angina (SA). Methods and Results —Peripheral blood lymphocytes were collected at the time of hospitalization and after 2 and 12 weeks. Cytokine-producing CD4 + and CD8 + T cells were quantified by 3-color flow cytometry after stimulation with phorbol myristate acetate and ionomycin. UA was associated with an increased number of CD4 + and CD8 + T cells producing IFN-γ, whereas patients with SA had higher frequencies of IL-2 + and IL-4 + CD4 + T cells. Expansion of the IFN-γ + T-cell population in UA persisted for at least 3 months. Increased production of IFN-γ in UA could be attributed to the expansion of an unusual subset of T cells, CD4 + CD28 null T cells. Conclusions —Patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFN-γ production, suggesting that monocyte activation and acute phase responses are consequences of T-cell activation. IFN-γ is produced by CD4 + CD28 null T cells, which are expanded in UA and distinctly low in SA and controls. The emergence of CD4 + CD28 null T cells may result from persistent antigenic stimulation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CD28− T cells produce high levels of IFN-γ, have cytotoxic functions, and accumulate in inflammatory lesions.
“CD28− T cells are high producers for interferon-γ (IFN-γ), display cytotoxic functions and accumulate in inflammatory lesions [21–26].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes
Epstein, F. H., Fuster, V., Badimón, L., Badimón, L., & Chesebro, J. H. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201303260506 · Cited by 3,804 · see citing works
The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes
Epstein, F. H., Fuster, V., Badimón, L., Badimón, J. J., & Chesebro, J. H. (1992) · New England Journal of Medicine · doi:10.1056/nejm199201233260406 · Cited by 2,713 · see citing works
The Prognostic Value of C-Reactive Protein and Serum Amyloid A Protein in Severe Unstable Angina
Liuzzo, G., Biasucci, L. M., Gallimore, J. R., Grillo, R. L., Rebuzzi, A. G., Pepys, M. B., & Maseri, A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199408183310701 · Cited by 2,354 · see citing works
Self-citationvan der Wal, A. C., Becker, A. E., van der Loos, C. M., & Das, P. K. (1994) · Circulation · doi:10.1161/01.cir.89.1.36 · Cited by 1,906 · see citing works
Production of C-reactive protein and risk of coronary events in stable and unstable angina
Haverkate, E., Thompson, S. G., Pyke, S., Gallimore, J. R., & Mark B Pepys Group (1997) · The Lancet · doi:10.1016/s0140-6736(96)07591-5 · Cited by 1,511 · see citing works
Detection of activated T lymphocytes in the human atherosclerotic plaque.
Hansson, G. K., Holm, J., & Jonasson, L. (1989) · PubMed · Cited by 743 · see citing works
Elevated Levels of Interleukin-6 in Unstable Angina
Biasucci, L. M., Vitelli, A., Liuzzo, G., Altamura, S., Caligiuri, G., Monaco, C. G., Rebuzzi, A. G., Ciliberto, G., & Maseri, A. (1996) · Circulation · doi:10.1161/01.cir.94.5.874 · Cited by 738 · see citing works
Self-citationKovanen, P. T., Kaartinen, M., & Paavonen, T. (1995) · Circulation · doi:10.1161/01.cir.92.5.1084 · Cited by 615 · see citing works
Schmidt, D., Goronzy, J. J., & Weyand, C. M. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118638 · Cited by 482 · see citing works
Self-citationMazzone, A., Servi, S. D., Ricevuti, G., Mazzucchelli, I., Fossati, G., Pasotti, D., Bramucci, E., ANGOLI, L., Marsico, F., & Specchia, G. (1993) · Circulation · doi:10.1161/01.cir.88.2.358 · Cited by 338 · see citing works
Mackay, K., Mack, C., Brophy, S. T., & Călin, A. (1998) · Arthritis & Rheumatism · doi:10.1002/1529-0131(199812)41:12 · Cited by 327 · see citing works
Self-citationExpansion of unusual CD4+ T cells in severe rheumatoid arthritis
Martens, P. B., Goronzy, J. J., Schaid, D. J., & Weyand, C. M. (1997) · Arthritis & Rheumatism · doi:10.1002/art.1780400615 · Cited by 290 · see citing works
Self-citationFunctional properties of CD4+CD28− T cells in the aging immune system
Weyand, C. M., Brandes, J. C., Schmidt, D., Fulbright, J. W., & Goronzy, J. J. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(97)00161-9 · Cited by 201 · see citing works
Self-citationRole of inflammation in coronary plaque disruption.
Buja, L. M., & Willerson, J. T. (1994) · Circulation · doi:10.1161/01.cir.89.1.503 · Cited by 197 · see citing works
The Repertoire of CD4+ CD28− T Cells in Rheumatoid Arthritis
Schmidt, D., Martens, P. B., Weyand, C. M., & Goronzy, J. J. (1996) · Molecular Medicine · doi:10.1007/bf03401644 · Cited by 135 · see citing works
Self-citationJude, B., Agraou, B., McFadden, E., Susen, S., Bauters, C., Lepelley, P., Vanhaesbroucke, C., Devos, P., Cosson, A., & Asseman, P. (1994) · Circulation · doi:10.1161/01.cir.90.4.1662 · Cited by 124 · see citing works
Co‐stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28− T cells
Park, W., Weyand, C. M., Schmidt, D., & Goronzy, J. J. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270507 · Cited by 102 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Namekawa T, Wagner UG, Goronzy JJ, Weyand CM. Functional subsets of CD4 T cells in rheumatoid synovitis. Arthritis Rheum. 1998;41: 2108 -2116.
- Weyand CM, Brandes J, Schmidt D, Fulbright JW, Goronzy JJ. Func- tional properties of CD4ϩCD28-T cells in the aging immune system. Mech Ageing Dev. 1998;102:131-147.
Cited by
Sorted by citations
Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways
Tedgui, A., & Mallat, Z. (2006) · Physiological Reviews · doi:10.1152/physrev.00024.2005 · Cited by 1,701 · see citing works
“Furthermore, patients with UA are characterized by a perturbation of the functional T-cell repertoire with a bias toward IFNproduction (409).”
BackgroundThe immunology of rheumatoid arthritis
Weyand, C. M., & Goronzy, J. J. (2020) · Nature Immunology · doi:10.1038/s41590-020-00816-x · Cited by 821 · see citing works
Self-citationCD28− T cells: their role in the age-associated decline of immune function
Weng, N., Akbar, A. N., & Goronzy, J. J. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.03.013 · Cited by 629 · see citing works
“In addition, CD4 CD28− T cells play a role in the vascular inflammation in atherosclerotic diseases that lead to plaque instability, acute coronary syndromes and stroke [85,86].”
BackgroundSelf-citationExpression of Interleukin-18 in Human Atherosclerotic Plaques and Relation to Plaque Instability
Mallat, Z., Corbaz, A., Scoazec, A., Besnard, S., Lesèche, G., Chvatchko, Y., & Tedgui, A. (2001) · Circulation · doi:10.1161/hc3901.096721 · Cited by 632 · see citing works
Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes.
Liuzzo, G., Goronzy, J. J., Yang, H., Kopecky, S. L., Holmes, D. R., Frye, R. L., & Weyand, C. M. (2000) · Circulation · doi:10.1161/01.cir.101.25.2883 · Cited by 552 · see citing works
Self-citationAging of the Immune System. Mechanisms and Therapeutic Targets
Weyand, C. M., & Goronzy, J. J. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201602-095aw · Cited by 554 · see citing works
Self-citationCrea, F., & Libby, P. (2017) · Circulation · doi:10.1161/circulationaha.117.029870 · Cited by 488 · see citing works
The Role of Pro-Inflammatory Cytokines in the Pathogenesis of Cardiovascular Disease
Zhang, H., & Dhalla, N. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021082 · Cited by 409 · see citing works
“Patients with unstable angina showed higher numbers of CD4+ and CD8+ T-cells producing IFN-γ than patients with stable angina [126].”
BackgroundPasceri, V., & Yeh, E. T. H. (1999) · Circulation · doi:10.1161/01.cir.100.21.2124 · Cited by 381 · see citing works
van Leeuwen, E. M. M., Remmerswaal, E. B. M., Vossen, M. T. M., Rowshani, A. T., Dillen, P. M. E. W., van Lier, R. A. W., & ten Berge, I. J. M. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.1834 · Cited by 369 · see citing works
“Enhanced numbers of CD4 CD28 cells have been found in patients with RA and with cardiovascular diseases (2, 3, 5, 6).”
BackgroundT-cell-mediated lysis of endothelial cells in acute coronary syndromes
Nakajima, T., Schulte, S., Warrington, K. J., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2002) · Circulation · doi:10.1161/hc0502.103348 · Cited by 356 · see citing works
Self-citationdel Rincón, I., Williams, K., D, M. P. S. M., Freeman, G. L., O’Leary, D. H., & Escalante, A. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11078 · Cited by 353 · see citing works
Yen, J., Moore, B. E., Nakajima, T. E., Scholl, D., Schaid, D. J., Weyand, C. M., & Goronzy, J. J. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.193.10.1159 · Cited by 335 · see citing works
“A direct role of CD4 1 CD28 null T cells in vascular injury has been suggested because these cells are also a risk factor for inflammation and rupturing of atherosclerotic plaques in acute coronary syndromes (13, 14).”
BackgroundInfluentialSelf-citationPPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes
Marx, N., Kehrle, B., Kohlhammer, K., Grüb, M., Köenig, W., Hombach, V., Libby, P., & Plutzky, J. (2002) · Circulation Research · doi:10.1161/01.res.0000014225.20727.8f · Cited by 331 · see citing works
Kumeda, Y., Inaba, M., Goto, H., Nagata, M., Henmi, Y., Furumitsu, Y., Ishimura, E., Inui, K., Yutani, Y., Miki, T., et al. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10269 · Cited by 307 · see citing works
Mallat, Z., Gojová, A., Brun, V., Esposito, B., Fournier, N., Cottrez, F., Tedgui, A., & Groux, H. (2003) · Circulation · doi:10.1161/01.cir.0000089083.61317.a1 · Cited by 305 · see citing works
Teichert-Kuliszewska, K. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(00)00231-5 · Cited by 290 · see citing works
Ray, K. K., & Cannon, C. P. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.05.086 · Cited by 273 · see citing works
Down-Regulation of CD28 Expression by TNF-α
Bryl, E., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3231 · Cited by 264 · see citing works
“Interestingly, CD4 T cells that completely lack expression of CD28 have been found in unusually high frequencies among patients with various inflammatory conditions such as rheumatoid arthritis (RA)(4) (1, 8), Wegener’s granulomatosis (9), and unstable coronary artery disease (10).”
BackgroundSelf-citationInflammation: A pivotal link between autoimmune diseases and atherosclerosis
Abou‐Raya, A., & Abou‐Raya, S. (2006) · Autoimmunity Reviews · doi:10.1016/j.autrev.2005.12.006 · Cited by 264 · see citing works
“Similarly, in patients with RA, a stable expansion of CD4+ T cell subset that lacks expression of the CD28 molecule and that secretes predominantly Th1 cytokines (that promote endothelial injury) has been described in the peripheral blood and may contribute to early atherosclerotic damage in these patients [13,16– 18].”
BackgroundInfluentialCD4+CD28− T Lymphocytes Contribute to Early Atherosclerotic Damage in Rheumatoid Arthritis Patients
Gerli, R., Schillaci, G., Giordano, A., Bartoloni, E., Bistoni, O., Vaudo, G., Marchesi, S., Pirro, M., Ragni, F., Shoenfeld, Y., et al. (2004) · Circulation · doi:10.1161/01.cir.0000131450.66017.b3 · Cited by 254 · see citing works
Robertson, A.-K. L., & Hansson, G. K. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000245830.29764.84 · Cited by 252 · see citing works
Pathogenesis of Acute Coronary Syndromes
Crea, F., & Liuzzo, G. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.07.064 · Cited by 247 · see citing works
“Indeed, we have consistently observed that patients with ACS have an increased frequency of autoaggressive CD4 T cells characterized by defective cell surface expression of CD28, a major costimulatory molecule critically involved in determining the outcome of antigen recognition by T cells (32,33).”
BackgroundSelf-citationUnusual CD4+CD28nullT Lymphocytes and Recurrence of Acute Coronary Events
Liuzzo, G., Biasucci, L. M., Trotta, G., Brugaletta, S., Pinnelli, M., Giannuario, G. D., Rizzello, V., Rebuzzi, A. G., Rumi, C., Maseri, A., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.06.040 · Cited by 236 · see citing works
Self-citationCardiorheumatology: cardiac involvement in systemic rheumatic disease
Prasad, M., Hermann, J., Gabriel, S. E., Weyand, C. M., Mulvagh, S. L., Mankad, R., Oh, J. K., Matteson, E. L., & Lerman, A. (2014) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2014.206 · Cited by 213 · see citing works
Self-citationImmunometabolism in the development of rheumatoid arthritis
Weyand, C. M., & Goronzy, J. J. (2020) · Immunological Reviews · doi:10.1111/imr.12838 · Cited by 193 · see citing works
Self-citationGoronzy, J. J., & Weyand, C. M. (2003) · Arthritis Research · doi:10.1186/ar974 · Cited by 199 · see citing works
Self-citationPlatelet-leukocyte interplay during vascular disease
Schrottmaier, W. C., Mußbacher, M., Salzmann, M., & Assinger, A. (2020) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2020.04.018 · Cited by 187 · see citing works
Widlansky, M. E., Wang, J., Shenouda, S. M., Hagen, T. M., SMITH, A. R. W., Kizhakekuttu, T. J., Kluge, M. A., Weihrauch, D., Gutterman, D. D., & Vita, J. A. (2010) · Translational research · doi:10.1016/j.trsl.2010.04.001 · Cited by 180 · see citing works
Tackling ischaemic heart disease in rheumatoid arthritis
Kitas, G. D. (2003) · British journal of rheumatology · doi:10.1093/rheumatology/keg175 · Cited by 180 · see citing works
Sato, K., Niessner, A., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20051062 · Cited by 175 · see citing works
“A previous study has shown that these T cell abnormalities are not short-lived, likely precede the acute event, and certainly persist over time (12).”
BackgroundSelf-citationGoronzy, J. J., & Weyand, C. M. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00245.x · Cited by 175 · see citing works
Self-citationEnhanced T-Helper-1 Lymphocyte Activation Patterns in Acute Coronary Syndromes
Methe, H., Brunner, S., Wiegand, D., Näbauer, M., Koglin, J., & Edelman, E. R. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.03.040 · Cited by 174 · see citing works
Clonality and longevity of CD4+CD28null T cells are associated with defects in apoptotic pathways
Vallejo, A. N., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.11.6301 · Cited by 169 · see citing works
“higher levels of IFNg (3, 4), giving them the ability to function as”
BackgroundSelf-citationT-cell aging in rheumatoid arthritis
Weyand, C. M., Yang, Z., & Goronzy, J. J. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000011 · Cited by 164 · see citing works
Self-citationImmunosenescence, autoimmunity, and rheumatoid arthritis
Weyand, C. M., Fulbright, J. W., & Goronzy, J. J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00090-1 · Cited by 161 · see citing works
Self-citationThe role of T and B cells in human atherosclerosis and atherothrombosis
Ammirati, E., Moroni, F., Magnoni, M., & Camici, P. G. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12477 · Cited by 157 · see citing works
Deeks, S. G., Verdin, E. M., & McCune, J. M. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.05.004 · Cited by 158 · see citing works
“The abundance of potentially senescent cells (as defined by the lack of CD28 expression or the presence of CD57 on lymphocytes) correlates with a variety of negative outcomes, such as decreased vaccine responsiveness in the elderly, autoimmunity, frailty, reduction in overall TCR repertoire, cardiovascular disease, po…”
BackgroundHeat-Shock Protein 60-Reactive CD4 + CD28 null T Cells in Patients With Acute Coronary Syndromes
Zal, B., Kaski, J. C., Arno, G., Akiyu, J. P., Xu, Q., Cole, D., Whelan, M., Russell, N., Madrigal, J. A., Dodi, I. A., et al. (2004) · Circulation · doi:10.1161/01.cir.0000118476.29352.2a · Cited by 155 · see citing works
Raza, K., Thambyrajah, J., Townend, J., Exley, A., Hortas, C., Filer, A. D., Carruthers, D. M., & BACON, P. A. (2000) · Circulation · doi:10.1161/01.cir.102.13.1470 · Cited by 152 · see citing works
Warrington, K. J., Kent, P. D., Frye, R. L., Lymp, J. F., Kopecky, S. L., Goronzy, J. J., & Weyand, C. M. (2005) · Arthritis Research & Therapy · doi:10.1186/ar1775 · Cited by 150 · see citing works
“This may be due, at least in part, to the expansion of nonclassic CD4+ T cells that have previously been implicated in the pathogenesis of CAD [6,9].”
BackgroundResultInfluentialSelf-citationImmunosenescence: signaling pathways, diseases and therapeutic targets
Fu, Y., Wang, B., Alu, A., Hong, W., Hong, L., He, X., Shi, H., Cheng, P., & Yang, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02371-z · Cited by 157 · see citing works
Atherosclerotic Plaque Stability—What Determines the Fate of a Plaque?
Halvorsen, B. L., Otterdal, K., Dahl, T. B., Skjelland, M., Gullestad, L. L., Øie, E., & Aukrust, P. (2008) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2008.09.001 · Cited by 146 · see citing works
“First, a number of studies have colocalized CD4 T cells and IFN-γ within human and mouse atherosclerotic lesions, suggesting the predominance of Th1 cells in atherogenesis.(62,63) More recently, high levels of IL-12 and IL-18 mRNA and protein have also been detected in atherosclerotic plaques further suggesting a Th1…”
BackgroundElevated White Blood Cell Count and Carotid Plaque Thickness
Elkind, M. S. V., Cheng, J., Boden-Albala, B. M., Paik, M. C., & Sacco, R. L. (2001) · Stroke · doi:10.1161/01.str.32.4.842 · Cited by 144 · see citing works
Long-Term Prognostic Value of Neopterin
Ray, K. K., Morrow, D. A., Sabatine, M. S., Shui, A. M., Rifai, N., Cannon, C. P., & D, E. B. M. (2007) · Circulation · doi:10.1161/circulationaha.106.666511 · Cited by 137 · see citing works
Pathogenic features of CD4+CD28– T cells in immune disorders
Broux, B., Markovic-Plese, S., Stinissen, P., & Hellings, N. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.06.003 · Cited by 131 · see citing works
Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes
Song, C., Hsu, K., Yamen, E., Yan, W., Fock, J., Witting, P. K., Geczy, C. L., & Freedman, B. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2009.05.007 · Cited by 133 · see citing works
Functional profile of activated dendritic cells in unstable atherosclerotic plaque
Erbel, C., Sato, K., Meyer, F. B., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2006) · Basic Research in Cardiology · doi:10.1007/s00395-006-0636-x · Cited by 132 · see citing works
“Evidence has been presented that such T cells are in a state of activation, suggesting that they have been exposed to stimulatory signals in the tissue microenvironment [27, 42].”
Self-citationCD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation
Warrington, K. J., Vallejo, A. N., Weyand, C. M., & Goronzy, J. J. (2003) · Blood · doi:10.1182/blood-2002-08-2574 · Cited by 132 · see citing works
Self-citationCardiovascular co-morbidity in rheumatic diseases
Turesson, C. (2008) · Vascular Health and Risk Management · doi:10.2147/vhrm.s2453 · Cited by 130 · see citing works
“Increased levels of CD4 + CD28 null T-cells have been demonstrated in patients with chronic infl ammatory disorders such as RA (Schmidt et al 1996), especially those with severe, systemic disease (Michel et al 2007), and unstable coronary artery disease (Liuzzo et al 1999).”
Neutrophil–Lymphocyte Ratio as a Predictor of Major Adverse Cardiac Events Among Diabetic Population
Azab, B. N., Chainani, V., Shah, N. N., & McGinn, J. T. (2012) · Angiology · doi:10.1177/0003319712455216 · Cited by 128 · see citing works
Nakajima, T., Goek, O., Zhang, X., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2003) · Circulation Research · doi:10.1161/01.res.0000082333.58263.58 · Cited by 127 · see citing works
Self-citationCD4+CD28null T cells in coronary artery disease: when helpers become killers
Dumitriu, I. E., Araguás, E. T., BABOONIAN, C., & Kaski, J. C. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn248 · Cited by 125 · see citing works
Phenotypic and Functional Characterization of CD4 T Cells Expressing Killer Ig-Like Receptors
van Bergen, J., Thompson, A., van der Slik, A. R., Ottenhoff, T. H. M., Gussekloo, J., & Koning, F. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.11.6719 · Cited by 124 · see citing works
“CD28 CD4 T cells have been reported to play a role in rheumatoid arthritis and acute coronary syndromes (17, 34).”
BackgroundInflammation and coronary artery disease
Tiong, A. Y., & Brieger, D. B. (2005) · American Heart Journal · doi:10.1016/j.ahj.2004.12.019 · Cited by 119 · see citing works
Inflammation, Atherosclerosis, and Stroke
Elkind, M. S. V. (2006) · The Neurologist · doi:10.1097/01.nrl.0000215789.70804.b0 · Cited by 120 · see citing works
“Further evidence has suggested that this marker may predict stroke, as well.(49) Other studies have found that circulating levels of specific leukocytes, such as the CD4 CD28 subset of T lymphocytes, also present in rheumatoid arthritis, may be associated with unstable angina and recurrence after first stroke.”
BackgroundGiubilato, S., Liuzzo, G., Brugaletta, S., Pitocco, D., Graziani, F., Smaldone, C., Montone, R. A., Pazzano, V., Pedicino, D., Biasucci, L. M., et al. (2011) · European Heart Journal · doi:10.1093/eurheartj/ehq499 · Cited by 119 · see citing works
Self-citationNew insights into the pathogenesis of rheumatoid arthritis
Weyand, C. M. (2000) · Lara D. Veeken · doi:10.1093/oxfordjournals.rheumatology.a031491 · Cited by 119 · see citing works
“In addition, a possible direct involvement of CD4+CD28null T cells in vascular injury is suggested by their emergence in patients with rupture of atherosclerotic plaque and acute coronary syndrome [20].”
BackgroundSelf-citationCentral Role of Thrombospondin-1 in the Activation and Clonal Expansion of Inflammatory T Cells
Vallejo, A. N., Muegge, L. O., Klimiuk, P. A., Weyand, C. M., & Goronzy, J. J. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.6.2947 · Cited by 118 · see citing works
“These unusual cells were first reported among rheumatoid arthritis (RA) 5 patients (10) and have now been found in other inflammatory syndromes such as those associated with ischemic heart disease (11), Wegener’s granulomatosis (12), and in Chagas’ disease (13).”
BackgroundSelf-citationPatients With Acute Coronary Syndrome Show Oligoclonal T-Cell Recruitment Within Unstable Plaque
Palma, R. D., Galdo, F. D., Abbate, G., Massimo Chiariello, A., Calabrò, R., Forte, L., Cimmino, G., Papa, M. F., Russo, M. G., Ambrosio, G., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.537712 · Cited by 117 · see citing works
Cheng, X. C., Liao, Y., Ge, H., Li, B., Zhang, J., Yuan, J., Wang, M., Liu, Y., Guo, Z., Chen, J., et al. (2005) · Journal of Clinical Immunology · doi:10.1007/s10875-005-4088-0 · Cited by 116 · see citing works
Dumitriu, I. E., Baruah, P., Finlayson, C. J., Loftus, I. M., Antunes, R. D. S., Lim, P. O., Bunce, N. H., & Kaski, J. C. (2012) · Circulation Research · doi:10.1161/circresaha.111.261933 · Cited by 116 · see citing works
Widespread Myocardial Inflammation and Infarct-Related Artery Patency
Abbate, A., Bonanno, E., Mauriello, A., Bussani, R., Biondi‐Zoccai, G., Liuzzo, G., Leone, A. M., Silvestri, F., Dobrina, A., Baldi, F., et al. (2004) · Circulation · doi:10.1161/01.cir.0000133316.92316.81 · Cited by 116 · see citing works
Self-citationThe life (and death) of CD 4 + CD 28 null T cells in inflammatory diseases
Dumitriu, I. E. (2015) · Immunology · doi:10.1111/imm.12506 · Cited by 111 · see citing works
Cheng, X. C., Liao, Y., Ge, H., Li, B., Zhang, J., Yuan, J., Wang, M., Liu, Y., Guo, Z., Chen, J., et al. (2014) · Journal of Clinical Immunology · doi:10.1007/s10875-014-0062-z · Cited by 109 · see citing works
Broadley, I., Pera, A., Morrow, G., Davies, K. A., & Kern, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00195 · Cited by 103 · see citing works
“Clin Exp Rheumatol (1992) 10(2):161–4.”
BackgroundResultInfluentialInterleukin 12 Induces T-Cell Recruitment Into the Atherosclerotic Plaque
Zhang, X., Niessner, A., Nakajima, T. E., Ma-Krupa, W., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M. (2006) · Circulation Research · doi:10.1161/01.res.0000204452.46568.57 · Cited by 106 · see citing works
Self-citationFormation of the Killer Ig-Like Receptor Repertoire on CD4+CD28null T Cells
Snyder, M. R., Muegge, L., Offord, C. P., O’Fallon, W. M., Bajzer, Ž., Weyand, C. M., & Goronzy, J. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.8.3839 · Cited by 104 · see citing works
“However, KIRs are regularly found on CD4 CD28 T cells, a subset of T cells that is expanded in patients with RA (29) and patients with unstable angina (30), but is only infrequently found in healthy individuals.”
BackgroundSelf-citationExpansion of cytolytic CD4+CD28− T cells in end-stage renal disease
Betjes, M. G. H., Huisman, M., Weimar, W. W., & Litjens, N. H. R. (2008) · Kidney International · doi:10.1038/ki.2008.301 · Cited by 103 · see citing works
“The circulating CD4posCD28null T-cell subset is enriched in the blood of patients with acute coronary syndromes and typically produces high levels of interferon-g (IFN-g).(10) Plaque-infiltrating CD4 T cells, which are associated with plaque vulnerability for rupture, are likely recruited from this circulating CD4posC…”
BackgroundAccelerated immunosenescence in rheumatoid arthritis: impact on clinical progression
Bauer, M. E. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00178-w · Cited by 102 · see citing works
Immune Aging- A Mechanism in Autoimmune Disease
Zheng, Y., Liu, Q., Goronzy, J., & Weyand, C. (2023) · Seminars in Immunology · doi:10.1016/j.smim.2023.101814 · Cited by 95 · see citing works
Self-citationSangiorgi, G., Mauriello, A., Bonanno, E., Oxvig, C., Conover, C. A., Christiansen, M., Trimarchi, S., Rampoldi, V., Holmes, D. R., Schwartz, R. S., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.11.086 · Cited by 101 · see citing works
Molecular Fingerprint of Interferon-γ Signaling in Unstable Angina
Liuzzo, G., Vallejo, A. N., Kopecky, S. L., Frye, R. L., Holmes, D. R., Goronzy, J. J., & Weyand, C. M. (2001) · Circulation · doi:10.1161/01.cir.103.11.1509 · Cited by 101 · see citing works
Self-citationImmune Aging and Rheumatoid Arthritis
Goronzy, J. J., Shao, L., & Weyand, C. M. (2010) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2010.03.001 · Cited by 99 · see citing works
“frequently have an expanded population of T-effector cells that have lost the CD28 molecule.(75) They contribute to vascular damage by releasing proinflammatory cytokines(76) and also by cytotoxic activity toward vascular endothelial(77) and smooth muscle cells.”
BackgroundSelf-citationLaman, J. D., Schoneveld, A. H., Moll, F. L., van Meurs, M., & Pasterkamp, G. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02432-3 · Cited by 98 · see citing works
Characterization of CD8+CD57+ T cells in patients with acute myocardial infarction
Yu, H. T., Youn, J., Lee, J., Park, S., Chi, H.-S., Lee, J., Choi, C., Park, S., Choi, D., Ha, J., et al. (2014) · Cellular and Molecular Immunology · doi:10.1038/cmi.2014.74 · Cited by 98 · see citing works
Liuzzo, G., Angiolillo, D. J., Buffon, A., Rizzello, V., Colizzi, C., Ginnetti, F., Biasucci, L. M., & Maseri, A. (2001) · Circulation · doi:10.1161/01.cir.103.18.2236 · Cited by 97 · see citing works
“PTCA/CABG 11 (58)/5 (26) 4 (31)/6 (46) 0.”
Self-citationRelative risk of cardiovascular events in patients with rheumatoid arthritis
DeMaria, A. N. (2002) · The American Journal of Cardiology · doi:10.1016/s0002-9149(02)02235-x · Cited by 97 · see citing works
Immune System and Atherosclerotic Disease
Shimada, K. (2009) · Circulation Journal · doi:10.1253/circj.cj-09-0277 · Cited by 93 · see citing works
Leukocyte count predicts outcome after ischemic stroke: The Northern Manhattan Stroke Study
Elkind, M. S. V., Cheng, J., Rundek, T., Boden-Albala, B. M., & Sacco, R. L. (2004) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2004.07.004 · Cited by 93 · see citing works
Increased Th1 activity in patients with coronary artery disease
Fernandes, J. L., Mamoni, R. L., Orford, J. L., Garcia, C., Selwyn, A. P., Coelho, O. R., & Blotta, M. H. S. L. (2004) · Cytokine · doi:10.1016/j.cyto.2004.01.007 · Cited by 92 · see citing works
Clinical implications of inflammation for cardiovascular primary prevention
Libby, P., & Crea, F. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq022 · Cited by 91 · see citing works
Molecular Basis for the Loss of CD28 Expression in Senescent T Cells
Vallejo, A. N., Bryl, E., Klarskov, K., Naylor, S., Weyand, C. M., & Goronzy, J. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207352200 · Cited by 91 · see citing works
Self-citationAn Inflammatory Pathway of IFN-γ Production in Coronary Atherosclerosis
Ranjbaran, H., Sokol, S. I., Gallo, A. E., Eid, R. E., Yakimov, A. O., D’Alessio, A., Kapoor, J. R., Akhtar, S., Howes, C., Aslan, M., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.1.592 · Cited by 89 · see citing works
“IFN- , a key proatherogenic cytokine, is expressed in arterial plaques (12, 13) and by circulating T cells (8, 14) in patients with coronary atherosclerosis.”
BackgroundAge-associated changes within CD4+ T cells
Kovaiou, R. D., & Grubeck-Loebenstein, B. (2006) · Immunology Letters · doi:10.1016/j.imlet.2006.07.006 · Cited by 90 · see citing works
T cell costimulation by fractalkine‐expressing synoviocytes in rheumatoid arthritis
Sawai, H., Park, Y. W., Roberson, J., Imai, T., Goronzy, J. J., & Weyand, C. M. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21140 · Cited by 87 · see citing works
Self-citationT Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease
Shirakawa, K., & Sano, M. (2021) · Cells · doi:10.3390/cells10092435 · Cited by 87 · see citing works
Peripheral Frequency of CD4+ CD28− Cells in Acute Ischemic Stroke
Tuttolomondo, A., Pecoraro, R., Casuccio, A., Raimondo, D. D., Buttà, C., Clemente, G., Corte, V. D., Guggino, G., Arnao, V., Maida, C. D., et al. (2015) · Medicine · doi:10.1097/md.0000000000000813 · Cited by 85 · see citing works
High Prevalence of Circulating CD4+CD28−T-Cells in Patients With Small Abdominal Aortic Aneurysms
Duftner, C., Seiler, R., Klein-Weigel, P. F., Göbel, H., Goldberger, C., Ihling, C. H., Fraedrich, G., & Schirmer, M. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000167520.41436.c0 · Cited by 85 · see citing works
Elevated pro-inflammatory CD4 + CD28 − lymphocytes and stroke recurrence and death
Nadareishvili, Z., Li, H., Wright, V., Maric, D., Warach, S. J., Hallenbeck, J. M., Dambrosia, J., Barker, J. L., & Baird, A. E. (2004) · Neurology · doi:10.1212/01.wnl.0000142260.61443.7c · Cited by 84 · see citing works
Requirements for CD8 T-cell migration into the human arterial wall
Gewaltig, J., Kummer, M., Koella, C., Cathomas, G., & Biedermann, B. C. (2008) · Human Pathology · doi:10.1016/j.humpath.2008.04.018 · Cited by 83 · see citing works
“Our data confirm other reports [8-10,26] that conventional atherosclerosis belongs to the list of human diseases in which CD8 T cells are quantitatively important.”
BackgroundResultInfluentialRelative elevation in baseline leukocyte count predicts first cerebral infarction
Elkind, M. S. V., Sciacca, R. R., Boden-Albala, B. M., Rundek, T., Paik, M. C., & Sacco, R. L. (2005) · Neurology · doi:10.1212/01.wnl.0000165989.12122.49 · Cited by 83 · see citing works
The immunoinhibitory PD-1/PD-L1 pathway in inflammatory blood vessel disease
Weyand, C. M., Berry, G. J., & Goronzy, J. J. (2017) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ma0717-283 · Cited by 83 · see citing works
Self-citationT cell senescence and cardiovascular diseases
Yu, H. T., Park, S., Shin, E., & Lee, W. (2015) · Clinical and Experimental Medicine · doi:10.1007/s10238-015-0376-z · Cited by 83 · see citing works
Takeda, H., Spatz, M., Ruetzler, C. A., McCarron, R. M., Becker, K. J., & Hallenbeck, J. M. (2002) · Stroke · doi:10.1161/01.str.0000029821.82531.8b · Cited by 82 · see citing works
Mechanisms of Disease: the evolving role of regulatory T cells in atherosclerosis
George, J. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1279 · Cited by 81 · see citing works
Adaptive Immunity Dysregulation in Acute Coronary Syndromes
Flego, D., Liuzzo, G., Weyand, C. M., & Crea, F. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.08.036 · Cited by 81 · see citing works
Self-citationEosinophil cationic protein: A new biomarker of coronary atherosclerosis
Niccoli, G., Ferrante, G., Cosentino, N., Conte, M., Belloni, F., Marino, M., Bacà, M., Montone, R. A., Sabato, V., Schiavino, D., et al. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.02.038 · Cited by 81 · see citing works
Vallejo, A. N. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.01.005 · Cited by 83 · see citing works
T-Cell Immunity in Acute Coronary Syndromes
Weyand, C. M., Goronzy, J. J., Liuzzo, G., Kopecky, S. L., Holmes, D. R., & Frye, R. L. (2001) · Mayo Clinic Proceedings · doi:10.4065/76.10.1011 · Cited by 81 · see citing works
Self-citation
- Authors
- Liuzzo, G., Kopecky, S. L., Frye, R. L., Fallon, W. M. O., Maseri, A., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- From the Departments of Medicine (G.L., S.L.K., R.L.F., J.J.G., C.M.W.) and Biostatistics (W.M.O.), Mayo Clinic, Rochester, Minn; and the Division of Cardiology (A.M.), Catholic University, Rome, Italy.
- Venue
- Circulation
- Published
- 1999-11-23
- Volume
- 100
- Issue
- 21
- Pages
- 2135-2139
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1976292294
- Cited by
- 398
- References
- 17
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 12 · 2023: 8 · 2022: 12 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 10 · 2017: 18 · 2016: 17 · 2015: 17 · 2014: 14 · 2013: 16 · 2012: 21
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- unstable angina, stable angina, T cell receptor repertoire, interferon-gamma, CD4+CD28- T cells, CD8+ T cells, CD4+ T cells, cytokine production, monocyte activation, acute phase response, interleukin-6, interleukin-2, IL-4
- MeSH terms
- Adult, Aged, Angina, Unstable, Female, Humans, Interferon-gamma, Male, Middle Aged, Monocytes, T-Lymphocytes, CD4 Antigens, CD28 Antigens
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
