The aim of this study was to evaluate CD25+ and Lag3+ T regulatory subpopulations in patients with critical carotid artery stenosis (CAS) and Stanford-A acute aortic dissection (AAD). CD25+ and Lag3+ were measured in 36 patients affected by CAS and 24 patients with Stanford type A AAD. Based on neurological symptoms, patients affected by CAS were further divided in 25 asymptomatic (CAS-A) and 11 symptomatic (CAS-S) subjects. Twenty-five patients with traditional cardiovascular risk factors (RF), matched for age and sex, were used as control group. Interleukin (IL)-10, IL-6 and transforming growth factor-β-levels were also measured. CD25+ T cells were significantly increased in CAS-S versus CAS-A (p > 0.05), AAD (p > 0.05) and RF (p > 0.05). Moreover, a significant increase in Lag3+ Tregs was observed in CAS e CAS-S versus AAD (p < 0.05) and RF (p < 0.05), whereas no significant difference was observed between CAS-S and CAS-A. IL-6 was higher in AAD compared to the other groups. Patients with neurological symptoms display a peculiar expansion of CD25+ T cells, strongly confirming a relationship between ischemic brain damage and this regulatory subpopulation, whereas Lag3+ Tregs early distinguish CAS from AAD and probably exert protective actions against aortic wall rupture throughout their anti-inflammatory functions.
Regulatory T cells Carotid artery stenosis Acute aortic dissection
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Compliance with ethical standards
Conflict of interest
The authors have no actual or potential conflict of interest to declare, including any financial, personal or other relationships with other people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.
The study was performed according to the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the Faculty of Medicine.
Written informed consent was obtained from each patient or from an authorized family member.
Roncarolo MG, Battaglia M. Regulatory T-cell immunotherapy for tolerance to self antigens and alloantigens in humans. Nat Rev Immunol. 2007;7:585–98.CrossRefGoogle Scholar
Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87.CrossRefGoogle Scholar
Sakaguchi S, Sakaguchi N, Asano M, et al. Immunologic self tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155:1151–64.Google Scholar
Groux H, O’Garra A, Bigler M, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997;389:737–42.CrossRefGoogle Scholar
Lim HW, Hillsamer P, Banham AH, et al. Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol. 2005;175:4180–3.CrossRefGoogle Scholar
Kim HJ, Verbinnen B, Tang X, et al. Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance. Nature. 2010;467:328–32.CrossRefPubMedCentralGoogle Scholar
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–61.CrossRefGoogle Scholar
Sakaguchi S, Powrie F. Emerging challenges in regulatory T cell function and biology. Science. 2007;17:627–9.CrossRefGoogle Scholar
Bacchetta R, Sartirana C, Levings MK, et al. Growth and expansion of human T regulatory type 1 cells are independent from TCR activation but require exogenous cytokines. Eur J Immunol. 2002;32:2237–45.CrossRefGoogle Scholar
Gagliani N, Magnani CF, Huber S, et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013;19:739–46.CrossRefGoogle Scholar
Okamura T, Fujio K, Shibuya M, et al. CD4+ CD25− LAG3+ regulatory T cells controlled by the transcription factor Egr-2. Proc Natl Acad Sci USA. 2009;106:13974–9.CrossRefGoogle Scholar
Okamura T, Sumitomo S, Morita K, et al. TGF-β3-expressing CD4+ CD25− LAG3+ regulatory T cells control humoral immune responses. Nat Commun. 2015;6:6329.CrossRefPubMedCentralGoogle Scholar
Gisterå A, Hansson GK. The immunology of atherosclerosis. Nat Rev Nephrol. 2017;13:368–80.CrossRefGoogle Scholar
Kleinschnitz C, Kraft P, Dreykluft A, et al. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature. Blood. 2013;121:679–91.CrossRefPubMedCentralGoogle Scholar
Del Porto F, Cifani N, Proietta M, et al. Regulatory T CD4+ CD25+ lymphocytes increase in symptomatic carotid artery stenosis. Ann Med. 2017;49:283–90.CrossRefGoogle Scholar
Kaplan A, Altara R, Eid A, et al. Update on the protective role of regulatory T Cells in myocardial infarction: a promising therapy to repair the heart. J Cardiovasc Pharmacol. 2016;68:401–13.CrossRefGoogle Scholar
Raman G, Moorthy D, Hadar N, et al. Management strategies for asymptomatic carotid stenosis: a systematic review and meta-analysis. Ann Intern Med. 2013;158:676–85.CrossRefGoogle Scholar
Nakachi S, Sumitomo S, Tsuchida Y, et al. Interleukin-10-producing LAG3+ regulatory T cells are associated with disease activity and abatacept treatment in rheumatoid arthritis. Arthritis Res Ther. 2017;19:97.CrossRefPubMedCentralGoogle Scholar
Del Porto F, Proietta M, Tritapepe L, et al. Inflammation and immune response in acute aortic dissection. Ann Med. 2010;42:622–9.CrossRefGoogle Scholar