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Published in: BMC Cardiovascular Disorders 1/2023

Open Access 01-12-2023 | Heart Failure | Research

Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy

Authors: Sílvia Martins, Natália António, Tiago Carvalheiro, Paula Laranjeira, Ricardo Rodrigues, Lino Gonçalves, Cândida Tomaz, Artur Paiva

Published in: BMC Cardiovascular Disorders | Issue 1/2023

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Abstract

Background

T cells have been implicated in the development and progression of inflammatory processes in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure (HF) patients.

Methods

Thirty-nine HF patients were evaluated before CRT (T0) and six months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry.

Results

T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08 ± 0.50 versus (heart failure patients (HFP)-T0: 0.69 ± 0.40, P = 0.022) and remaining diminished after CRT (HFP-T6: 0.61 ± 0.29, P = 0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52 ± 12.55 versus NR: 24.71 ± 11.66, P = 0.006). After CRT, HF patients presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50 ± 16.62 versus R: 61.47 ± 20.54, P = 0.014; and HG: 40.62 ± 15.36 versus R: 52.39 ± 18.66, P = 0.049, respectively).

Conclusion

The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response. Even after CRT, it seems that the inflammatory condition underlying CHF continues to evolve with the progression of the disease. This could be due, at least in part, to the inability to restore Treg cells levels.
Trial registration: Observational and prospective study with no trial registration.
Appendix
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Literature
1.
go back to reference Jessup M, Brozena S. Heart failure-reply. N Engl J Med. 2003;349(10):1004–1004. Jessup M, Brozena S. Heart failure-reply. N Engl J Med. 2003;349(10):1004–1004.
2.
go back to reference Straburzynska-Migaj E, Kaluzna-Oleksy M, Maggioni AP, Grajek S, Opolski G, Ponikowski P, et al. Patients with heart failure and concomitant chronic obstructive pulmonary disease participating in the Heart Failure Pilot Survey (ESC-HF Pilot)-Polish population. Arch Med Sci. 2015;11(4):743–50.PubMedPubMedCentralCrossRef Straburzynska-Migaj E, Kaluzna-Oleksy M, Maggioni AP, Grajek S, Opolski G, Ponikowski P, et al. Patients with heart failure and concomitant chronic obstructive pulmonary disease participating in the Heart Failure Pilot Survey (ESC-HF Pilot)-Polish population. Arch Med Sci. 2015;11(4):743–50.PubMedPubMedCentralCrossRef
3.
go back to reference Heymans S, Hirsch E, Anker SD, Aukrust P, Balligand JL, Cohen-Tervaert JW, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2009;11(2):119–29.PubMedPubMedCentralCrossRef Heymans S, Hirsch E, Anker SD, Aukrust P, Balligand JL, Cohen-Tervaert JW, et al. Inflammation as a therapeutic target in heart failure? A scientific statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2009;11(2):119–29.PubMedPubMedCentralCrossRef
4.
go back to reference Stanciu AE, Vatasescu RG, Stanciu MM, Iorgulescu C, Vasile AI, Dorobantu M. Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects. Clin Biochem. 2013;46(3):230–4.PubMedCrossRef Stanciu AE, Vatasescu RG, Stanciu MM, Iorgulescu C, Vasile AI, Dorobantu M. Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects. Clin Biochem. 2013;46(3):230–4.PubMedCrossRef
5.
go back to reference Tang T-T, Yuan J, Zhu Z-F, Zhang W-C, Xiao H, Xia N, et al. Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol. 2012;107(1):1–17.CrossRef Tang T-T, Yuan J, Zhu Z-F, Zhang W-C, Xiao H, Xia N, et al. Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol. 2012;107(1):1–17.CrossRef
6.
go back to reference Blanton RM, Carrillo-Salinas FJ, Alcaide P. T-cell recruitment to the heart: friendly guests or unwelcome visitors? Am J Physiol Heart Circ Physiol. 2019;317(1):H124–40.PubMedPubMedCentralCrossRef Blanton RM, Carrillo-Salinas FJ, Alcaide P. T-cell recruitment to the heart: friendly guests or unwelcome visitors? Am J Physiol Heart Circ Physiol. 2019;317(1):H124–40.PubMedPubMedCentralCrossRef
7.
go back to reference Yndestad A, Kristian Damås J, Geir Eiken H, Holm T, Haug T, Simonsen S, Frøland SS, Gullestad L, Aukrust P. Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure. Cardiovasc Res. 2002;54(1):175–82.PubMedCrossRef Yndestad A, Kristian Damås J, Geir Eiken H, Holm T, Haug T, Simonsen S, Frøland SS, Gullestad L, Aukrust P. Increased gene expression of tumor necrosis factor superfamily ligands in peripheral blood mononuclear cells during chronic heart failure. Cardiovasc Res. 2002;54(1):175–82.PubMedCrossRef
8.
go back to reference Yndestad A. Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res. 2003;60(1):141–6.PubMedCrossRef Yndestad A. Enhanced expression of inflammatory cytokines and activation markers in T-cells from patients with chronic heart failure. Cardiovasc Res. 2003;60(1):141–6.PubMedCrossRef
9.
go back to reference Li N, Bian H, Zhang J, Li X, Ji X, Zhang Y. The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. Clin Chim Acta. 2010;411(23–24):1963–8.PubMedCrossRef Li N, Bian H, Zhang J, Li X, Ji X, Zhang Y. The Th17/Treg imbalance exists in patients with heart failure with normal ejection fraction and heart failure with reduced ejection fraction. Clin Chim Acta. 2010;411(23–24):1963–8.PubMedCrossRef
10.
go back to reference Fukunaga T, Soejima H, Irie A, Sugamura K, Oe Y, Tanaka T, et al. Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2007;100(3):483–8.PubMedCrossRef Fukunaga T, Soejima H, Irie A, Sugamura K, Oe Y, Tanaka T, et al. Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 2007;100(3):483–8.PubMedCrossRef
11.
go back to reference Tang TT, Zhu YC, Dong NG, Zhang S, Cai J, Zhang LX, et al. Pathologic T-cell response in ischaemic failing hearts elucidated by T-cell receptor sequencing and phenotypic characterization. Eur Heart J. 2019;40(48):3924–33.PubMedCrossRef Tang TT, Zhu YC, Dong NG, Zhang S, Cai J, Zhang LX, et al. Pathologic T-cell response in ischaemic failing hearts elucidated by T-cell receptor sequencing and phenotypic characterization. Eur Heart J. 2019;40(48):3924–33.PubMedCrossRef
12.
go back to reference Cai YH, Ma ZJ, Lu XY, He EL, You MY. Study on the effect and mechanism of the dysfunction of CD4(+) T cells in the disease process of chronic cardiac failure. Asian Pac J Trop Med. 2016;9(7):682–7.PubMedCrossRef Cai YH, Ma ZJ, Lu XY, He EL, You MY. Study on the effect and mechanism of the dysfunction of CD4(+) T cells in the disease process of chronic cardiac failure. Asian Pac J Trop Med. 2016;9(7):682–7.PubMedCrossRef
13.
go back to reference Bansal SS, Ismahil MA, Goel M, Zhou G, Rokosh G, Hamid T, Prabhu SD. Dysfunctional and proinflammatory regulatory T-lymphocytes are essential for adverse cardiac remodeling in ischemic cardiomyopathy. Circulation. 2019;139(2):206–21.PubMedPubMedCentralCrossRef Bansal SS, Ismahil MA, Goel M, Zhou G, Rokosh G, Hamid T, Prabhu SD. Dysfunctional and proinflammatory regulatory T-lymphocytes are essential for adverse cardiac remodeling in ischemic cardiomyopathy. Circulation. 2019;139(2):206–21.PubMedPubMedCentralCrossRef
14.
go back to reference Yamaoka-Tojo M, Tojo T, Inomata T, Machida Y, Osada K, Izumi T. Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure. J Card Fail. 2002;8(1):21–7.PubMedCrossRef Yamaoka-Tojo M, Tojo T, Inomata T, Machida Y, Osada K, Izumi T. Circulating levels of interleukin 18 reflect etiologies of heart failure: Th1/Th2 cytokine imbalance exaggerates the pathophysiology of advanced heart failure. J Card Fail. 2002;8(1):21–7.PubMedCrossRef
16.
go back to reference Santos-Zas I, Lemarié J, Zlatanova I, Cachanado M, Seghezzi J-C, Benamer H, et al. Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling. Nat Commun. 2021;12(1):1–13.CrossRef Santos-Zas I, Lemarié J, Zlatanova I, Cachanado M, Seghezzi J-C, Benamer H, et al. Cytotoxic CD8+ T cells promote granzyme B-dependent adverse post-ischemic cardiac remodeling. Nat Commun. 2021;12(1):1–13.CrossRef
17.
go back to reference Almeida-Morais L, Abreu A, Oliveira M, Silva Cunha P, Rodrigues I, Portugal G, et al. Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: the paradox of functional and echocardiographic response. Rev Port Cardiol (Engl Ed). 2018;37(2):105–13.PubMedCrossRef Almeida-Morais L, Abreu A, Oliveira M, Silva Cunha P, Rodrigues I, Portugal G, et al. Impact of cardiac resynchronization therapy on inflammatory biomarkers and cardiac remodeling: the paradox of functional and echocardiographic response. Rev Port Cardiol (Engl Ed). 2018;37(2):105–13.PubMedCrossRef
18.
go back to reference Ptaszynska-Kopczynska K, Szpakowicz A, Marcinkiewicz-Siemion M, Lisowska A, Waszkiewicz E, Witkowski M, et al. Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy. Arch Med Sci. 2017;13(5):1069–77.PubMedCrossRef Ptaszynska-Kopczynska K, Szpakowicz A, Marcinkiewicz-Siemion M, Lisowska A, Waszkiewicz E, Witkowski M, et al. Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy. Arch Med Sci. 2017;13(5):1069–77.PubMedCrossRef
19.
go back to reference Osmancik P, Herman D, Stros P, Linkova H, Vondrak K, Paskova E. Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy. Cardiology. 2013;124(3):190–8.PubMedCrossRef Osmancik P, Herman D, Stros P, Linkova H, Vondrak K, Paskova E. Changes and prognostic impact of apoptotic and inflammatory cytokines in patients treated with cardiac resynchronization therapy. Cardiology. 2013;124(3):190–8.PubMedCrossRef
21.
go back to reference Ramani GV, Uber PA, Mehra MR. Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc. 2010;5:180–95.CrossRef Ramani GV, Uber PA, Mehra MR. Chronic heart failure: contemporary diagnosis and management. Mayo Clin Proc. 2010;5:180–95.CrossRef
23.
go back to reference Martins S, Carvalheiro T, Laranjeira P, Martinho A, Elvas L, Gonçalves L, Tomaz C, António N, Paiva A. Impact of cardiac resynchronization therapy on circulating IL-17 producing cells in patients with advanced heart failure. J Interv Card Electrophysiol. 2019;54(3):257–65.PubMedCrossRef Martins S, Carvalheiro T, Laranjeira P, Martinho A, Elvas L, Gonçalves L, Tomaz C, António N, Paiva A. Impact of cardiac resynchronization therapy on circulating IL-17 producing cells in patients with advanced heart failure. J Interv Card Electrophysiol. 2019;54(3):257–65.PubMedCrossRef
25.
go back to reference McComb S, Thiriot A, Akache B, Krishnan L, Stark F: Introduction to the immune system. In: Immunoproteomics. Springer; 2019; 1–24. McComb S, Thiriot A, Akache B, Krishnan L, Stark F: Introduction to the immune system. In: Immunoproteomics. Springer; 2019; 1–24.
26.
go back to reference Choi KJ, Tsomidou C, Lerakis S, Madanieh R, Vittorio TJ, Kosmas CE. Lipid interventions in aortic valvular disease. Am J Med Sci. 2015;350(4):313–9.PubMedCrossRef Choi KJ, Tsomidou C, Lerakis S, Madanieh R, Vittorio TJ, Kosmas CE. Lipid interventions in aortic valvular disease. Am J Med Sci. 2015;350(4):313–9.PubMedCrossRef
27.
go back to reference Wienecke LM, Cohen S, Bauersachs J, Mebazaa A, Chousterman BG. Immunity and inflammation: the neglected key players in congenital heart disease? Heart Fail Rev. 2021;5:1–15. Wienecke LM, Cohen S, Bauersachs J, Mebazaa A, Chousterman BG. Immunity and inflammation: the neglected key players in congenital heart disease? Heart Fail Rev. 2021;5:1–15.
28.
go back to reference Borgel D, Bianchini E, Lasne D, Pascreau T, Saller F. Inflammation in deep vein thrombosis: a therapeutic target? Hematology. 2019;24(1):742–50.PubMedCrossRef Borgel D, Bianchini E, Lasne D, Pascreau T, Saller F. Inflammation in deep vein thrombosis: a therapeutic target? Hematology. 2019;24(1):742–50.PubMedCrossRef
29.
go back to reference Montagnana M, Fava C, Arosio E, Degan M, Tommasoli RM, De Marchi S, et al. Inflammation and platelet activation in peripheral arterial occlusive disease. Int J Angiol. 2007;16(03):84–8.PubMedPubMedCentralCrossRef Montagnana M, Fava C, Arosio E, Degan M, Tommasoli RM, De Marchi S, et al. Inflammation and platelet activation in peripheral arterial occlusive disease. Int J Angiol. 2007;16(03):84–8.PubMedPubMedCentralCrossRef
30.
go back to reference Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–40.PubMedCrossRef Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–40.PubMedCrossRef
31.
go back to reference Lord JM, Midwinter MJ, Chen Y-F, Belli A, Brohi K, Kovacs EJ, Koenderman L, Kubes P, Lilford RJ. The systemic immune response to trauma: an overview of pathophysiology and treatment. The Lancet. 2014;384(9952):1455–65.CrossRef Lord JM, Midwinter MJ, Chen Y-F, Belli A, Brohi K, Kovacs EJ, Koenderman L, Kubes P, Lilford RJ. The systemic immune response to trauma: an overview of pathophysiology and treatment. The Lancet. 2014;384(9952):1455–65.CrossRef
32.
go back to reference Dutton RP. Inflammation after surgical trauma: bleeding or clotting? Anesth Analg. 2021;132(1):80–1.PubMedCrossRef Dutton RP. Inflammation after surgical trauma: bleeding or clotting? Anesth Analg. 2021;132(1):80–1.PubMedCrossRef
33.
go back to reference Garraud O, Hamzeh-Cognasse H, Laradi S, Pozzetto B, Cognasse F. Blood transfusion and inflammation as of yesterday, today and tomorrow. Transfus Clin Biol. 2015;22(3):168–77.PubMedCrossRef Garraud O, Hamzeh-Cognasse H, Laradi S, Pozzetto B, Cognasse F. Blood transfusion and inflammation as of yesterday, today and tomorrow. Transfus Clin Biol. 2015;22(3):168–77.PubMedCrossRef
34.
go back to reference Kalantar-Zadeh K, Stenvinkel P, Pillon L, Kopple JD. Inflammation and nutrition in renal insufficiency. Adv Ren Replace Ther. 2003;10(3):155–69.PubMedCrossRef Kalantar-Zadeh K, Stenvinkel P, Pillon L, Kopple JD. Inflammation and nutrition in renal insufficiency. Adv Ren Replace Ther. 2003;10(3):155–69.PubMedCrossRef
36.
go back to reference Larkin CM, Santos-Martinez M-J, Ryan T, Radomski MW. Sepsis-associated thrombocytopenia. Thromb Res. 2016;141:11–6.PubMedCrossRef Larkin CM, Santos-Martinez M-J, Ryan T, Radomski MW. Sepsis-associated thrombocytopenia. Thromb Res. 2016;141:11–6.PubMedCrossRef
37.
go back to reference Nadeau-Vallée M, Obari D, Palacios J, Brien M-È, Duval C, Chemtob S, Girard S. Sterile inflammation and pregnancy complications: a review. Reproduction. 2016;152(6):R277–92.PubMedCrossRef Nadeau-Vallée M, Obari D, Palacios J, Brien M-È, Duval C, Chemtob S, Girard S. Sterile inflammation and pregnancy complications: a review. Reproduction. 2016;152(6):R277–92.PubMedCrossRef
38.
go back to reference Raja SG, Berg GA. Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence. J Card Surg. 2007;22(5):445–55.PubMedCrossRef Raja SG, Berg GA. Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence. J Card Surg. 2007;22(5):445–55.PubMedCrossRef
39.
go back to reference Wang H, Liu Z, Shao J, Lin L, Jiang M, Wang L, et al. Immune and inflammation in acute coronary syndrome: molecular mechanisms and therapeutic implications. J Immunol Res. 2020;2:20. Wang H, Liu Z, Shao J, Lin L, Jiang M, Wang L, et al. Immune and inflammation in acute coronary syndrome: molecular mechanisms and therapeutic implications. J Immunol Res. 2020;2:20.
40.
go back to reference Cristóvão G, Milner J, Sousa P, Ventura M, Cristóvão J, Elvas L, et al. Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits. Stem Cell Res Ther. 2020;11(1):1–8.CrossRef Cristóvão G, Milner J, Sousa P, Ventura M, Cristóvão J, Elvas L, et al. Improvement in circulating endothelial progenitor cells pool after cardiac resynchronization therapy: increasing the list of benefits. Stem Cell Res Ther. 2020;11(1):1–8.CrossRef
41.
go back to reference Kydd AC, Khan FZ, Ring L, Pugh PJ, Virdee MS, Dutka DP. Development of a multiparametric score to predict left ventricular remodelling and prognosis after cardiac resynchronization therapy. Eur J Heart Fail. 2014;16(11):1206–13.PubMedCrossRef Kydd AC, Khan FZ, Ring L, Pugh PJ, Virdee MS, Dutka DP. Development of a multiparametric score to predict left ventricular remodelling and prognosis after cardiac resynchronization therapy. Eur J Heart Fail. 2014;16(11):1206–13.PubMedCrossRef
42.
go back to reference Carvalheiro T, Velada I, Valado A, Mendes F, Martinho A, Antonio N, et al. Phenotypic and functional alterations on inflammatory peripheral blood cells after acute myocardial infarction. J Cardiovasc Transl Res. 2012;5(3):309–20.PubMedCrossRef Carvalheiro T, Velada I, Valado A, Mendes F, Martinho A, Antonio N, et al. Phenotypic and functional alterations on inflammatory peripheral blood cells after acute myocardial infarction. J Cardiovasc Transl Res. 2012;5(3):309–20.PubMedCrossRef
43.
go back to reference Henriques A, Ines L, Couto M, Pedreiro S, Santos C, Magalhaes M, et al. Frequency and functional activity of Th17, Tc17 and other T-cell subsets in systemic lupus erythematosus. Cell Immunol. 2010;264(1):97–103.PubMedCrossRef Henriques A, Ines L, Couto M, Pedreiro S, Santos C, Magalhaes M, et al. Frequency and functional activity of Th17, Tc17 and other T-cell subsets in systemic lupus erythematosus. Cell Immunol. 2010;264(1):97–103.PubMedCrossRef
44.
go back to reference Banham AH. Cell-surface IL-7 receptor expression facilitates the purification of FOXP3(+) regulatory T cells. Trends Immunol. 2006;27(12):541–4.PubMedCrossRef Banham AH. Cell-surface IL-7 receptor expression facilitates the purification of FOXP3(+) regulatory T cells. Trends Immunol. 2006;27(12):541–4.PubMedCrossRef
45.
go back to reference Vetter TR, Mascha EJ. Unadjusted bivariate two-group comparisons: when simpler is better. Anesth Analg. 2018;126(1):338–42.PubMedCrossRef Vetter TR, Mascha EJ. Unadjusted bivariate two-group comparisons: when simpler is better. Anesth Analg. 2018;126(1):338–42.PubMedCrossRef
47.
go back to reference Xia N, Lu Y, Gu M, Li N, Liu M, Jiao J, et al. A unique population of regulatory T cells in heart potentiates cardiac protection from myocardial infarction. Circulation. 2020;142(20):1956–73.PubMedCrossRef Xia N, Lu Y, Gu M, Li N, Liu M, Jiao J, et al. A unique population of regulatory T cells in heart potentiates cardiac protection from myocardial infarction. Circulation. 2020;142(20):1956–73.PubMedCrossRef
48.
go back to reference Albany CJ, Trevelin SC, Giganti G, Lombardi G, Scotta C. Getting to the heart of the matter: the role of regulatory T-cells (Tregs) in cardiovascular disease (CVD) and atherosclerosis. Front Immunol. 2019;10:2795.PubMedPubMedCentralCrossRef Albany CJ, Trevelin SC, Giganti G, Lombardi G, Scotta C. Getting to the heart of the matter: the role of regulatory T-cells (Tregs) in cardiovascular disease (CVD) and atherosclerosis. Front Immunol. 2019;10:2795.PubMedPubMedCentralCrossRef
50.
go back to reference Xia N, Jiao J, Tang TT, Lv BJ, Lu YZ, Wang KJ, et al. Activated regulatory T-cells attenuate myocardial ischaemia/reperfusion injury through a CD39-dependent mechanism. Clin Sci (Lond). 2015;128(10):679–93.PubMedCrossRef Xia N, Jiao J, Tang TT, Lv BJ, Lu YZ, Wang KJ, et al. Activated regulatory T-cells attenuate myocardial ischaemia/reperfusion injury through a CD39-dependent mechanism. Clin Sci (Lond). 2015;128(10):679–93.PubMedCrossRef
51.
go back to reference Huber SA, Feldman AM, Sartini D. Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in tumor necrosis factor-alpha transgenic mice. Circ Res. 2006;99(10):1109–16.PubMedCrossRef Huber SA, Feldman AM, Sartini D. Coxsackievirus B3 induces T regulatory cells, which inhibit cardiomyopathy in tumor necrosis factor-alpha transgenic mice. Circ Res. 2006;99(10):1109–16.PubMedCrossRef
52.
go back to reference Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, Ertl G, Kerkau T, Frantz S. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ Res. 2014;115(1):55–67.PubMedCrossRef Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, Ertl G, Kerkau T, Frantz S. Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ Res. 2014;115(1):55–67.PubMedCrossRef
53.
go back to reference Matsumoto K, Ogawa M, Suzuki J-i, Hirata Y, Nagai R, Isobe M. Regulatory T lymphocytes attenuate myocardial infarction-induced ventricular remodeling in mice. Int Heart J. 2011;52(6):382–7.PubMedCrossRef Matsumoto K, Ogawa M, Suzuki J-i, Hirata Y, Nagai R, Isobe M. Regulatory T lymphocytes attenuate myocardial infarction-induced ventricular remodeling in mice. Int Heart J. 2011;52(6):382–7.PubMedCrossRef
54.
go back to reference Saxena A, Dobaczewski M, Rai V, Haque Z, Chen W, Li N, Frangogiannis NG. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol. 2014;307(8):H1233-1242.PubMedPubMedCentralCrossRef Saxena A, Dobaczewski M, Rai V, Haque Z, Chen W, Li N, Frangogiannis NG. Regulatory T cells are recruited in the infarcted mouse myocardium and may modulate fibroblast phenotype and function. Am J Physiol Heart Circ Physiol. 2014;307(8):H1233-1242.PubMedPubMedCentralCrossRef
55.
go back to reference Tang T-T, Ding Y-J, Liao Y-H, Yu X, Xiao H, Xie J-J, et al. Defective circulating CD4+ CD25+ Foxp3+ CD127low regulatory T-cells in patients with chronic heart failure. Cell Physiol Biochem. 2010;25(4–5):451–8.PubMedCrossRef Tang T-T, Ding Y-J, Liao Y-H, Yu X, Xiao H, Xie J-J, et al. Defective circulating CD4+ CD25+ Foxp3+ CD127low regulatory T-cells in patients with chronic heart failure. Cell Physiol Biochem. 2010;25(4–5):451–8.PubMedCrossRef
56.
go back to reference Kemp RA, Backstrom BT, Ronchese F. The phenotype of type 1 and type 2 CD8+ T cells activated in vitro is affected by culture conditions and correlates with effector activity. Immunology. 2005;115(3):315–24.PubMedPubMedCentralCrossRef Kemp RA, Backstrom BT, Ronchese F. The phenotype of type 1 and type 2 CD8+ T cells activated in vitro is affected by culture conditions and correlates with effector activity. Immunology. 2005;115(3):315–24.PubMedPubMedCentralCrossRef
57.
go back to reference Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135(3):626–35.PubMedCrossRef Annunziato F, Romagnani C, Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135(3):626–35.PubMedCrossRef
58.
go back to reference Annunziato F, Cosmi L, Liotta F, Maggi E, Romagnani S. Human Th1 dichotomy: origin, phenotype and biologic activities. Immunology. 2014;8:17. Annunziato F, Cosmi L, Liotta F, Maggi E, Romagnani S. Human Th1 dichotomy: origin, phenotype and biologic activities. Immunology. 2014;8:17.
59.
go back to reference Hamada H, Garcia-Hernandez Mde L, Reome JB, Misra SK, Strutt TM, McKinstry KK, Cooper AM, Swain SL, Dutton RW. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol. 2009;182(6):3469–81.PubMedCrossRef Hamada H, Garcia-Hernandez Mde L, Reome JB, Misra SK, Strutt TM, McKinstry KK, Cooper AM, Swain SL, Dutton RW. Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol. 2009;182(6):3469–81.PubMedCrossRef
60.
go back to reference Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol. 2005;95(11A):C6–C6 (discussion 38C-40C). Torre-Amione G. Immune activation in chronic heart failure. Am J Cardiol. 2005;95(11A):C6–C6 (discussion 38C-40C).
61.
go back to reference Brouwers C, Versteeg H, Meine M, Heijnen CJ, Kavelaars AM, Pedersen SS, Mommersteeg PM. Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy. Brain Behav Immun. 2014;40:211–8.PubMedCrossRef Brouwers C, Versteeg H, Meine M, Heijnen CJ, Kavelaars AM, Pedersen SS, Mommersteeg PM. Association between brain natriuretic peptide, markers of inflammation and the objective and subjective response to cardiac resynchronization therapy. Brain Behav Immun. 2014;40:211–8.PubMedCrossRef
62.
go back to reference Michelucci A, Ricciardi G, Sofi F, Gori AM, Pirolo F, Pieragnoli P, et al. Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy. J Card Fail. 2007;13(3):207–10.PubMedCrossRef Michelucci A, Ricciardi G, Sofi F, Gori AM, Pirolo F, Pieragnoli P, et al. Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy. J Card Fail. 2007;13(3):207–10.PubMedCrossRef
63.
go back to reference LappegÅRd KT, Bjørnstad H. Anti-inflammatory effect of cardiac resynchronization therapy. Pacing Clin Electrophysiol. 2006;29(7):753–8.PubMedCrossRef LappegÅRd KT, Bjørnstad H. Anti-inflammatory effect of cardiac resynchronization therapy. Pacing Clin Electrophysiol. 2006;29(7):753–8.PubMedCrossRef
64.
go back to reference Lappegard KT, Bjornstad H, Mollnes TE, Hovland A. Effect of cardiac resynchronization therapy on inflammation in congestive heart failure: a review. Scand J Immunol. 2015;82(3):191–8.PubMedCrossRef Lappegard KT, Bjornstad H, Mollnes TE, Hovland A. Effect of cardiac resynchronization therapy on inflammation in congestive heart failure: a review. Scand J Immunol. 2015;82(3):191–8.PubMedCrossRef
65.
go back to reference Gambardella J, Jankauskas SS, D’Ascia SL, Sardu C, Matarese A, Minicucci F, Mone P, Santulli G. Glycation of ryanodine receptor in circulating lymphocytes predicts the response to cardiac resynchronization therapy. J Heart Lung Transpl. 2022;41(4):438–41.CrossRef Gambardella J, Jankauskas SS, D’Ascia SL, Sardu C, Matarese A, Minicucci F, Mone P, Santulli G. Glycation of ryanodine receptor in circulating lymphocytes predicts the response to cardiac resynchronization therapy. J Heart Lung Transpl. 2022;41(4):438–41.CrossRef
66.
go back to reference Boriani G, Regoli F, Saporito D, Martignani C, Toselli T, Biffi M, et al. Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response. Peptides. 2006;27(7):1776–86.PubMedCrossRef Boriani G, Regoli F, Saporito D, Martignani C, Toselli T, Biffi M, et al. Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response. Peptides. 2006;27(7):1776–86.PubMedCrossRef
67.
go back to reference Tarquini R, Guerra CT, Porciani MC, Michelucci A, Padeletti M, Ricciardi G, Chiostri M, Jelic S, Padeletti L. Effects of cardiac resynchronization therapy on systemic inflammation and neurohormonal pathways in heart failure. Cardiol J. 2009;16(6):545–52.PubMed Tarquini R, Guerra CT, Porciani MC, Michelucci A, Padeletti M, Ricciardi G, Chiostri M, Jelic S, Padeletti L. Effects of cardiac resynchronization therapy on systemic inflammation and neurohormonal pathways in heart failure. Cardiol J. 2009;16(6):545–52.PubMed
68.
go back to reference Strassheim D, Dempsey EC, Gerasimovskaya E, Stenmark K, Karoor V. Role of inflammatory cell subtypes in heart failure. J Immunol Res. 2019;2019:2164017.PubMedPubMedCentralCrossRef Strassheim D, Dempsey EC, Gerasimovskaya E, Stenmark K, Karoor V. Role of inflammatory cell subtypes in heart failure. J Immunol Res. 2019;2019:2164017.PubMedPubMedCentralCrossRef
69.
go back to reference Frieler RA, Mortensen RM. Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling. Circulation. 2015;131(11):1019–30.PubMedPubMedCentralCrossRef Frieler RA, Mortensen RM. Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling. Circulation. 2015;131(11):1019–30.PubMedPubMedCentralCrossRef
Metadata
Title
Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy
Authors
Sílvia Martins
Natália António
Tiago Carvalheiro
Paula Laranjeira
Ricardo Rodrigues
Lino Gonçalves
Cândida Tomaz
Artur Paiva
Publication date
01-12-2023

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