Skip to main content
Top
Published in: Journal of Clinical Immunology 2/2010

01-03-2010

Th17 Cells Facilitate the Humoral Immune Response in Patients with Acute Viral Myocarditis

Authors: Jing Yuan, Ai-Lin Cao, Miao Yu, Qiong-Wen Lin, Xian Yu, Jing-Hui Zhang, Min Wang, He-Ping Guo, Yu-Hua Liao

Published in: Journal of Clinical Immunology | Issue 2/2010

Login to get access

Abstract

Background

Recently, the Th17 cell, a newly determined CD4+Th subset, was reported to participate in the inflammation of myocarditis combined with Th1 cells, and this study aimed to explore whether it was involved in the Th2 cell-mediated humoral immunity in viral myocarditis.

Methods

A total of 34 patients, including 16 acute viral myocarditis (AVMC) and 18 dilated cardiomyopathy (DCM) having a history of AVMC, were enrolled for this study besides 18 healthy volunteers.

Results

The frequencies of Th17 and Th1 cells, especially Th17 cells in AVMC patients, while those of Th1 and Th2 cells, especially Th2 cells in DCM group, were all increased significantly compared with those in healthy volunteers (P < 0.01), with no changes of Th2 cells in AVMC and Th17 cells in DCM groups. The similar results were also observed in Th cell cytokines (IL-17, INF-γ, and IL-4) and key transcript factors (RORγt, T-bet, and GATA-3). Meanwhile, antiheart antibodies (AHA) of IgG type were found in 15 (93.8%) patients with AVMC and ten (55.6%) cases with DCM, accompanied by the higher expression of IL-17R on B cells and the frequencies of B cells than those in healthy controls (P < 0.01 in AVMC and P < 0.05 in DCM, respectively) who had no AHA. Furthermore, both of the B cell activities in AVMC and DCM groups were elevated and positively correlated to serum IL-17 (R = 0.66, P < 0.01) and IL-4 (R = 0.47, P < 0.05) respectively, with no correlation to INF-γ.

Conclusions

It was Th17 cells but not Th2 cells that helped the B cells to produce AHA in AVMC and not until at the late phase of viral myocarditis could Th2 cells play the important role in mediating humoral response.
Literature
1.
2.
go back to reference Rose NR, Hill SL. The pathogenesis of postinfectious myocarditis. Clin Immunol Immunopathol. 1996;80:S92–9.CrossRefPubMed Rose NR, Hill SL. The pathogenesis of postinfectious myocarditis. Clin Immunol Immunopathol. 1996;80:S92–9.CrossRefPubMed
3.
go back to reference Mena I, Perry CM, Harkins S, Rodriguez F, Gebhard J, Whitton JL. The role of B lymphocytes in coxsachievirus B3 infection. Am J Pathol. 1999;155:1205–15.PubMed Mena I, Perry CM, Harkins S, Rodriguez F, Gebhard J, Whitton JL. The role of B lymphocytes in coxsachievirus B3 infection. Am J Pathol. 1999;155:1205–15.PubMed
4.
go back to reference Schwimmbeck PL, Bigalke B, Schulze K, Pauschinger M, Kuhl U, Schultheiss HP. The humoral immune responses in viral disease: characterization and pathophysiological significance of antibodies. Med Microbiol Immunol. 2004;193:2–3. Schwimmbeck PL, Bigalke B, Schulze K, Pauschinger M, Kuhl U, Schultheiss HP. The humoral immune responses in viral disease: characterization and pathophysiological significance of antibodies. Med Microbiol Immunol. 2004;193:2–3.
5.
go back to reference Christian K. Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant. 2008;23:816–9. Christian K. Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant. 2008;23:816–9.
6.
go back to reference Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.CrossRefPubMed Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol. 2005;6:1133–41.CrossRefPubMed
7.
go back to reference Atayar C, Poppema S, Blokzijl T, Harms G, Boot M, van den Berg A. Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin Lymphomas. Am J Pathol. 2005;166:127–30.PubMed Atayar C, Poppema S, Blokzijl T, Harms G, Boot M, van den Berg A. Expression of the T-cell transcription factors, GATA-3 and T-bet, in the neoplastic cells of Hodgkin Lymphomas. Am J Pathol. 2005;166:127–30.PubMed
8.
go back to reference Hwang SY, Kim HY. Expression of IL-1 7 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. Mol Cell. 2004;19:180–4. Hwang SY, Kim HY. Expression of IL-1 7 homologs and their receptors in the synovial cells of rheumatoid arthritis patients. Mol Cell. 2004;19:180–4.
9.
go back to reference Aranami T, Yamaura T. Th17 cells and autoimmune encephalomyelitis (EAE/MS). Allergol Int. 2008;57:115–20.CrossRefPubMed Aranami T, Yamaura T. Th17 cells and autoimmune encephalomyelitis (EAE/MS). Allergol Int. 2008;57:115–20.CrossRefPubMed
10.
go back to reference Garrett-Sinha LA, John S, Gaffen SL. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatal. 2008;20:519–25.CrossRef Garrett-Sinha LA, John S, Gaffen SL. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatal. 2008;20:519–25.CrossRef
11.
go back to reference Daniels MD, Hyland KV, Wang K, Engman DM. Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity. Autoimmunity. 2008;41:490–9.CrossRefPubMed Daniels MD, Hyland KV, Wang K, Engman DM. Recombinant cardiac myosin fragment induces experimental autoimmune myocarditis via activation of Th1 and Th17 immunity. Autoimmunity. 2008;41:490–9.CrossRefPubMed
12.
go back to reference Chang H, Hanawa H, Yoshida T, Hayashi M, Liu H, Ding L, et al. Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer. Circ J. 2008;72:813–9.CrossRefPubMed Chang H, Hanawa H, Yoshida T, Hayashi M, Liu H, Ding L, et al. Alteration of IL-17 related protein expressions in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer. Circ J. 2008;72:813–9.CrossRefPubMed
13.
go back to reference Hsu HC, Yang PA, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center developement in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.CrossRefPubMed Hsu HC, Yang PA, Wang J, Wu Q, Myers R, Chen J, et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center developement in autoimmune BXD2 mice. Nat Immunol. 2008;9:166–75.CrossRefPubMed
14.
go back to reference Doreau A, Belot A, Bastid J, Benjamin R, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10:778–87.CrossRefPubMed Doreau A, Belot A, Bastid J, Benjamin R, Trescol-Biemont MC, Ranchin B, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol. 2009;10:778–87.CrossRefPubMed
15.
go back to reference Task Force on Myocarditis and Cardiomyopathy of Chinese Journal of Cardiology Editor Committee: Reference standards for diagnosis of acute viral myocardits in adults. Chin J Cardiology. 1999;27:405–7. Task Force on Myocarditis and Cardiomyopathy of Chinese Journal of Cardiology Editor Committee: Reference standards for diagnosis of acute viral myocardits in adults. Chin J Cardiology. 1999;27:405–7.
16.
go back to reference Wynne J, Braunwald E. The cardiomyopathies and myocarditides. In: Braunwald E, Zipes DP, Libby P, editors. Heart disease. 6th ed. Philadelphia: Saunders; 2001. p. 1783–93. Wynne J, Braunwald E. The cardiomyopathies and myocarditides. In: Braunwald E, Zipes DP, Libby P, editors. Heart disease. 6th ed. Philadelphia: Saunders; 2001. p. 1783–93.
17.
go back to reference Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, et al. Report of the 1995 World Health Organization/ International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation. 1996;93:841–2.PubMed Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O'Connell J, et al. Report of the 1995 World Health Organization/ International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation. 1996;93:841–2.PubMed
18.
go back to reference Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127:89–97.PubMed Cheng X, Yu X, Ding YJ, Fu QQ, Xie JJ, Tang TT, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol. 2008;127:89–97.PubMed
19.
go back to reference Liao YH, Yuan J, Wang ZH, Cheng X, Zhang JH, Tian Y, et al. Infectious tolerance to ADP/ATP carrier peptides induced by anti-L3T4 monoclonal antibody in dilated cardiomyopathy mice. J Clin Immunol. 2005;25:376–84.CrossRefPubMed Liao YH, Yuan J, Wang ZH, Cheng X, Zhang JH, Tian Y, et al. Infectious tolerance to ADP/ATP carrier peptides induced by anti-L3T4 monoclonal antibody in dilated cardiomyopathy mice. J Clin Immunol. 2005;25:376–84.CrossRefPubMed
20.
go back to reference Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.CrossRefPubMed Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–33.CrossRefPubMed
21.
go back to reference Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–69.CrossRefPubMed Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000;100:655–69.CrossRefPubMed
22.
go back to reference Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89:587–96.CrossRefPubMed Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89:587–96.CrossRefPubMed
23.
go back to reference Caforio AL, Tona F, Bottaro S, Vinci A, Dequal G, Daliento L, et al. Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity. 2008;41:35–45.CrossRefPubMed Caforio AL, Tona F, Bottaro S, Vinci A, Dequal G, Daliento L, et al. Clinical implications of anti-heart autoantibodies in myocarditis and dilated cardiomyopathy. Autoimmunity. 2008;41:35–45.CrossRefPubMed
24.
go back to reference Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345–50.CrossRefPubMed Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8:345–50.CrossRefPubMed
25.
go back to reference Eriksson U, Kurrer MO, Sebald W, Brombacher F, Kopf M. Dual role of the IL-12/IFN-gamma axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN-gamma. J Immunol. 2001;167:5464–9.PubMed Eriksson U, Kurrer MO, Sebald W, Brombacher F, Kopf M. Dual role of the IL-12/IFN-gamma axis in the development of autoimmune myocarditis: induction by IL-12 and protection by IFN-gamma. J Immunol. 2001;167:5464–9.PubMed
26.
go back to reference Kehoe KE, Brown MA, Imani F. Double-stranded RNA regulates IL-4 expression. J Immunol. 2001;167:2496–501.PubMed Kehoe KE, Brown MA, Imani F. Double-stranded RNA regulates IL-4 expression. J Immunol. 2001;167:2496–501.PubMed
27.
go back to reference Rangachari M, Mauermann N, Marty RR, Dirnhofer S, Kurrer MO, Komnenovic V, et al. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin. J Exp Med. 2006;203:2009–19.CrossRefPubMed Rangachari M, Mauermann N, Marty RR, Dirnhofer S, Kurrer MO, Komnenovic V, et al. T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin. J Exp Med. 2006;203:2009–19.CrossRefPubMed
28.
go back to reference Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005;15:17–27.CrossRefPubMed Fairweather D, Frisancho-Kiss S, Rose NR. Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis. Rev Med Virol. 2005;15:17–27.CrossRefPubMed
29.
go back to reference Schwimmbeck PL, Bland NK, Schulthesis HP, Strauer BE. The possible value of synthetic peptides in the diagnosis and therapy of myocarditis and dilated cardiomyopathy. Eur Heart J. 1991;12(Suppl D):76–80.PubMed Schwimmbeck PL, Bland NK, Schulthesis HP, Strauer BE. The possible value of synthetic peptides in the diagnosis and therapy of myocarditis and dilated cardiomyopathy. Eur Heart J. 1991;12(Suppl D):76–80.PubMed
30.
go back to reference Liu HR, Zhao RR, Zhi JM, Wu BW, Fu ML. Screening of serum autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic acetylcholine receptors in 408 healthy subjects of varying ages. Autoimmunity. 1999;29:43–51.CrossRefPubMed Liu HR, Zhao RR, Zhi JM, Wu BW, Fu ML. Screening of serum autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic acetylcholine receptors in 408 healthy subjects of varying ages. Autoimmunity. 1999;29:43–51.CrossRefPubMed
Metadata
Title
Th17 Cells Facilitate the Humoral Immune Response in Patients with Acute Viral Myocarditis
Authors
Jing Yuan
Ai-Lin Cao
Miao Yu
Qiong-Wen Lin
Xian Yu
Jing-Hui Zhang
Min Wang
He-Ping Guo
Yu-Hua Liao
Publication date
01-03-2010
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 2/2010
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-009-9355-z

Other articles of this Issue 2/2010

Journal of Clinical Immunology 2/2010 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.