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Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyophthy

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Abstract

Inflammatory and immunological mechanisms are implicated in the development of idiopathic dilated cardiomyopathy (DCM). Since activated T lymphocytes express surface HLA-DR antigens, an increased level of these cells in the circulation could indicated an ongoing immune response. While the role of activated T lymphocytes in experimental myocarditis has been elucidated, the contribution of T lymphocyte activation in clinical DCM remains unclear. We therefore examined the role of T-cell activation in peripheral blood samples obtained from 10 patients with DCM (mean age, 49 ± 12 years) and from 10 age-matched healthy controls. Citrated whole blood was mixed with fluorescein isothiocyanate- or phycoerythrin-conjugated specific monoclonal antibodies and analyzed using a fluorescence-activated cell sorter (FACS). The ratio (%) of histocompatibility leukocyte antigen (HLA)-DR positive cells in the FACS gated lymphocyte population was significantly higher in DCM patients than in controls (7.9% ± 5.3% vs 2.0% ± 0.9%; P < 0.01). The expression of CD40L on T cells determined as mean fluorescence intensity (MFI) was also significantly higher in DCM patients than in controls (3.6 ± 2.1 vs 1.8 ± 0.4 MFI; P < 0.05). Furthermore, the ratios of T cells expressing HLA-DR and serum brain natriuretic peptide (BNP) levels closely correlated (P = 0.0008). We showed that HLA-DR on peripheral T cells significantly correlated with serum BNP levels and that high CD40L expression on T cells was concomitant with increased BNP levels (P < 0.05). Therefore the magnitude of T-cell expression, such as increased expression of HLA-DR and CD40L, contributes to myocardial dysfunction in DCM.

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References

  1. GW Dec V Fuster (1994) ArticleTitleIdiopathic dilated cardiomyopathy N Engl J Med 331 1564–1575 Occurrence Handle7969328 Occurrence Handle10.1056/NEJM199412083312307 Occurrence Handle1:STN:280:DyaK2M%2FlvFartw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. C Kawai (1999) ArticleTitleFrom myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future Circulation 199 1091–1100

    Google Scholar 

  3. BJ Friedman OY Grinberg NR Ratcliffe HM Swartz WF Hickey (1998) ArticleTitleAcute hemodynamic and coronary circulatory effects of experimental autoimmune myocarditis Heart Vessels 13 58–62 Occurrence Handle9987638 Occurrence Handle10.1007/BF01744587 Occurrence Handle1:STN:280:DyaK1M7kt1Wisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. F Kuethe RK Braun M Foerster Y Schlenker HH Sigusch C Kroegel HR Figulla (2006) ArticleTitleImmunopathogenesis of dilated cardiomyopathy. Evidence for the role of TH2-type CD4+ T lymphocytes and association with myocardial HLA-DR expression J Clin Immunol 26 33–39 Occurrence Handle16418801 Occurrence Handle10.1007/s10875-006-7585-x Occurrence Handle1:CAS:528:DC%2BD28XltVSgtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  5. HS Ko SM Fu RJ Winchester DT Yu HG Kunkel (1979) ArticleTitleIa determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells J Exp Med 150 246–255 Occurrence Handle88499 Occurrence Handle10.1084/jem.150.2.246 Occurrence Handle1:STN:280:DyaE1M3hsl2qtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  6. EG Engleman CJ Benike DJ Charron (1980) ArticleTitleIa antigen on peripheral blood mononuclear leukocytes in man. II. Functional studies of HLA-DR-positive T cells activated in mixed lymphocyte reactions J Exp Med 152 114s–126s Occurrence Handle6447741 Occurrence Handle1:STN:280:DyaL3M%2FgvVegug%3D%3D

    PubMed  CAS  Google Scholar 

  7. U Kühl M Noutsias B Seeberg HP Schultheiss (1996) ArticleTitleImmunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy Heart 75 295–300 Occurrence Handle8800996

    PubMed  Google Scholar 

  8. LE Rönnblom H Forsberg PE Evrin (1991) ArticleTitleIncreased level of HLA-DR-expressing T lymphocytes in peripheral blood from patients with idiopathic dilated cardiomyopathy Cardiology 78 161–167 Occurrence Handle1868494 Occurrence Handle10.1159/000174781

    Article  PubMed  Google Scholar 

  9. F Spertini T Chatila RS Geha (1992) ArticleTitleSignals delivered via MHC class II molecules synergize with signals delivered via TCR/CD3 to cause proliferation and cytokine gene expression in T cells J Immunol 149 65–70 Occurrence Handle1376752 Occurrence Handle1:CAS:528:DyaK38Xlt12nu7Y%3D

    PubMed  CAS  Google Scholar 

  10. A Svejgaard P Platz LP Ryder (1983) ArticleTitleHLA and disease 1982 – a survey Immunol Rev 70 193–218 Occurrence Handle6339368 Occurrence Handle10.1111/j.1600-065X.1983.tb00715.x Occurrence Handle1:STN:280:DyaL3s7lvFCksA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  11. L Fugger A Svejgaard (2000) ArticleTitleAssociation of MHC and rheumatoid arthritis. HLA-DR4 and rheumatoid arthritis: studies in mice and men Arthritis Res 2 208–211 Occurrence Handle11094431 Occurrence Handle10.1186/ar89 Occurrence Handle1:CAS:528:DC%2BD3cXlslyitr8%3D

    Article  PubMed  CAS  Google Scholar 

  12. JM Barker KJ Barriga L Yu D Miao HA Erlich JM Norris GS Eisenbarth M Rewers (2004) ArticleTitlePrediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY) J Clin Endocrinol Metab 89 3896–3902 Occurrence Handle15292324 Occurrence Handle10.1210/jc.2003-031887 Occurrence Handle1:CAS:528:DC%2BD2cXmslKmtbY%3D

    Article  PubMed  CAS  Google Scholar 

  13. JL Anderson JF Carlquist JR Lutz CW De Witt EH Hammond (1984) ArticleTitleHLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors Am J Cardiol 53 1326–1330 Occurrence Handle6585136 Occurrence Handle10.1016/0002-9149(84)90088-2 Occurrence Handle1:STN:280:DyaL2c7nsFOltw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  14. JF Carlquist RL Menlove MB Murray JB O'Connell JL Anderson (1991) ArticleTitleHLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies Circulation 83 515–522 Occurrence Handle1825038 Occurrence Handle1:STN:280:DyaK3M7itFKksg%3D%3D

    PubMed  CAS  Google Scholar 

  15. CJ Limas C Limas SH Kubo MT Olivari (1990) ArticleTitleAnti-beta-receptor antibodies in human dilated cardiomyopathy and correlation with HLA-DR antigens Am J Cardiol 65 483–487 Occurrence Handle2154917 Occurrence Handle10.1016/0002-9149(90)90815-I Occurrence Handle1:STN:280:DyaK3c7msVCiug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  16. G Torre-Amione S Kapadia C Benedict H Oral JB Young DL Mann (1996) ArticleTitleProinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD) J Am Coll Cardiol 27 1201–1206 Occurrence Handle8609343 Occurrence Handle10.1016/0735-1097(95)00589-7 Occurrence Handle1:STN:280:DyaK287osFymsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  17. V Henn JR Slupsky M Grafe I Anagnostopoulos R Forster G Muller-Berghaus RA Kroczek (1998) ArticleTitleCD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells Nature 391 591–594 Occurrence Handle9468137 Occurrence Handle10.1038/35393 Occurrence Handle1:CAS:528:DyaK1cXhtVSlsb8%3D

    Article  PubMed  CAS  Google Scholar 

  18. DL Mann (2002) ArticleTitleInflammatory mediators and the failing heart: past, present, and the foreseeable future Circ Res 91 988–998 Occurrence Handle12456484 Occurrence Handle10.1161/01.RES.0000043825.01705.1B Occurrence Handle1:CAS:528:DC%2BD38XoslOqt7o%3D

    Article  PubMed  CAS  Google Scholar 

  19. RJ Armitage CR Maliszewski MR Alderson KH Grabstein MK Spriggs WC Fanslow (1993) ArticleTitleCD40L: a multi-functional ligand Semin Immunol 5 401–412 Occurrence Handle7510138 Occurrence Handle10.1006/smim.1993.1046 Occurrence Handle1:CAS:528:DyaK2cXltF2rtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  20. RJ Noelle M Roy DM Shepherd I Stamenkovic JA Ledbetter A Aruffo (1992) ArticleTitleA 39-kDa protein on activated helper T cells binds CD40 and tradnsduces the signal for cognate activation of B cells Proc Natl Acad Sci USA 89 6550–6554 Occurrence Handle1378631 Occurrence Handle10.1073/pnas.89.14.6550 Occurrence Handle1:CAS:528:DyaK38Xlt12rsrg%3D

    Article  PubMed  CAS  Google Scholar 

  21. IS Grewal RA Flavell (1998) ArticleTitleCD40 and CD154 in cell-mediated immunity Annu Rev Immunol 16 111–135 Occurrence Handle9597126 Occurrence Handle10.1146/annurev.immunol.16.1.111 Occurrence Handle1:CAS:528:DyaK1cXislyitLg%3D

    Article  PubMed  CAS  Google Scholar 

  22. TM Foy A Aruffo J Bajorath JE Buhlmann RJ Noelle (1996) ArticleTitleImmune regulation by CD40 and its ligand GP39 Annu Rev Immunol 14 591–617 Occurrence Handle8717526 Occurrence Handle10.1146/annurev.immunol.14.1.591 Occurrence Handle1:CAS:528:DyaK28XitlCgtbk%3D

    Article  PubMed  CAS  Google Scholar 

  23. F Mach U Schonbeck JY Bonnefoy JS Pober P Libby (1997) ArticleTitleActivation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor Circulation 96 396–399 Occurrence Handle9244201 Occurrence Handle1:CAS:528:DyaK2sXltlShtbs%3D

    PubMed  CAS  Google Scholar 

  24. C Heeschen S Dimmeler CW Hamm MJ van den Brand E Boersma AM Zeiher ML Simoons (2003) ArticleTitleSoluble CD40 ligand in acute coronary syndromes N Engl J Med 348 1104–1111 Occurrence Handle12646667 Occurrence Handle10.1056/NEJMoa022600 Occurrence Handle1:CAS:528:DC%2BD3sXit1Smtbs%3D

    Article  PubMed  CAS  Google Scholar 

  25. N Varo JA de Lemos P Libby DA Morrow SA Murphy R Nuzzo CM Gibson CP Cannon E Braunwald U Schonbeck (2003) ArticleTitleSoluble CD40L: risk prediction after acute coronary syndromes Circulation 108 1049–1052 Occurrence Handle12912804 Occurrence Handle10.1161/01.CIR.0000088521.04017.13 Occurrence Handle1:CAS:528:DC%2BD3sXms1alur8%3D

    Article  PubMed  CAS  Google Scholar 

  26. Y Seko N Takahashi S Ishiyama T Nishikawa T Kasajima M Hiroe S Suzuki S Ishiwata S Kawai M Azuma H Yagita K Okumura Y Yazaki (1998) ArticleTitleExpression of costimulatory molecules B7-1, B7-2, and CD40 in the heart of patients with acute myocarditis and dilated cardiomyopathy Circulation 97 637–639 Occurrence Handle9495297 Occurrence Handle1:STN:280:DyaK1c7lsVKrtw%3D%3D

    PubMed  CAS  Google Scholar 

  27. T Ueland P Aukrust A Yndestad K Otterdal SS Froland K Dickstein J Kjekshus L Gullestad JK Damas (2005) ArticleTitleSoluble CD40 ligand in acute and chronic heart failure Eur Heart J 26 1101–1107 Occurrence Handle15716285 Occurrence Handle10.1093/eurheartj/ehi132 Occurrence Handle1:CAS:528:DC%2BD2MXht1CgsLrE

    Article  PubMed  CAS  Google Scholar 

  28. R Taniguchi Y Sato Y Nishio T Kimura T Kita (2006) ArticleTitleMeasurements of baseline and follow-up concentrations of cardiac troponin-T and brain natriuretic peptide in patients with heart failure from various etiologies Heart Vessels 21 344–349 Occurrence Handle17143708 Occurrence Handle10.1007/s00380-006-0909-1

    Article  PubMed  Google Scholar 

  29. HJ Why BT Meany PJ Richardson EG Olsen NE Bowles L Cunningham CA Freeke LC Archard (1994) ArticleTitleClinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy Circulation 89 2582–2589 Occurrence Handle8205668 Occurrence Handle1:STN:280:DyaK2c3msFeisg%3D%3D

    PubMed  CAS  Google Scholar 

  30. NE Bowles J Ni DL Kearney M Pauschinger HP Schultheiss R McCarthy J Hare JT Bricker KR Bowles JA Towbin (2003) ArticleTitleDetection of viruses in myocardial tissues by polymerase chain reaction. Evidence of adenovirus as a common cause of myocarditis in children and adults J Am Coll Cardiol 42 466–472 Occurrence Handle12906974 Occurrence Handle10.1016/S0735-1097(03)00648-X

    Article  PubMed  Google Scholar 

  31. A Matsumori Y Matoba S Sasayama (1995) ArticleTitleDilated cardiomyopathy associated with hepatitis C virus infection Circulation 92 2519–2525 Occurrence Handle7586353 Occurrence Handle1:STN:280:DyaK28%2FmvFaksA%3D%3D

    PubMed  CAS  Google Scholar 

  32. U Kühl M Pauschinger M Noutsias B Seeberg T Bock D Lassner W Poller R Kandolf HP Schultheiss (2005) ArticleTitleHigh prevalence of viral genomes and multiple viral infections in the myocardium of adults with idiopathic left ventricular dysfunction Circulation 111 887–893 Occurrence Handle15699250 Occurrence Handle10.1161/01.CIR.0000155616.07901.35

    Article  PubMed  Google Scholar 

  33. AL Caforio M Grazzini JM Mann PJ Keeling GF Bottazzo WJ McKenna S Schiaffino (1992) ArticleTitleIdentification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy Circulation 85 1734–1742 Occurrence Handle1533350 Occurrence Handle1:STN:280:DyaK383ktVOmtQ%3D%3D

    PubMed  CAS  Google Scholar 

  34. Y Magnusson G Wallukat F Waagstein A Hjalmarson J Hoebeke (1994) ArticleTitleAutoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta l-adrenoceptor with positive chronotropic effect Circulation 89 2760–2767 Occurrence Handle8205690 Occurrence Handle1:STN:280:DyaK2c3msFegsQ%3D%3D

    PubMed  CAS  Google Scholar 

  35. R Jahns V Boivin L Hein S Triebel CE Angermann G Ertl MJ Lohse (2004) ArticleTitleDirect evidence for a beta l-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy J Clin Invest 113 1419–1429 Occurrence Handle15146239 Occurrence Handle10.1172/JCI200420149 Occurrence Handle1:CAS:528:DC%2BD2cXktlCltrs%3D

    Article  PubMed  CAS  Google Scholar 

  36. T Okazaki Y Tanaka R Nishio T Mitsuiye A Mizoguchi J Wang M Ishida H Hiai A Matsumori N Minato T Honjo (2003) ArticleTitleAutoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice Nat Med 9 1477–1483 Occurrence Handle14595408 Occurrence Handle10.1038/nm955 Occurrence Handle1:CAS:528:DC%2BD3sXpt1Gksro%3D

    Article  PubMed  CAS  Google Scholar 

  37. H Nishimura T Okazaki Y Tanaka K Nakatani M Hara A Matsumori S Sasayama A Mizoguchi H Hiai N Minato T Honjo (2001) ArticleTitleAutoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice Science 291 319–322 Occurrence Handle11209085 Occurrence Handle10.1126/science.291.5502.319 Occurrence Handle1:CAS:528:DC%2BD3MXktlKlsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  38. GJ Freeman AJ Long Y Iwai K Bourque T Chernova H Nishimura LJ Fitz N Malenkovich T Okazaki MC Byrne HF Horton L Fouser L Carter V Ling MR Bowman BM Carreno M Collins CR Wood T Honjo (2000) ArticleTitleEngagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation J Exp Med 192 1027–1034 Occurrence Handle11015443 Occurrence Handle10.1084/jem.192.7.1027 Occurrence Handle1:CAS:528:DC%2BD3cXntFSlt7o%3D

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Atsuko Ueno, Kagari Murasaki, Nobuhisa Hagiwara & Hiroshi Kasanuki

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  1. Atsuko Ueno
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  2. Kagari Murasaki
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  3. Nobuhisa Hagiwara
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Correspondence to Kagari Murasaki.

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Ueno, A., Murasaki, K., Hagiwara, N. et al. Increases in circulating T lymphocytes expressing HLA-DR and CD40 ligand in patients with dilated cardiomyophthy. Heart Vessels 22, 316–321 (2007). https://doi.org/10.1007/s00380-007-0977-x

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  • DOI: https://doi.org/10.1007/s00380-007-0977-x

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