Circulation Research, Vol 75, 156-164, Copyright © 1994 by American Heart Association

ARTICLES

Transfer of human myocarditis into severe combined immunodeficiency mice

PL Schwimmbeck, C Badorff, HP Schultheiss and BE Strauer
Department of Internal Medicine/Cardiology, Heinrich-Heine University, Duesseldorf, Germany.

Severe combined immunodeficiency (SCID) mice possess neither T nor B lymphocytes and are thus suitable recipients for lymphocytes of different species. Because autoimmune mechanisms are suspected in the pathogenesis of myocarditis (MC), we attempted to determine whether peripheral blood lymphocytes (PBLs) from patients with MC could be transferred into SCID mice and whether they had an autoimmunologic effect. Groups of three mice each were injected intraperitoneally with up to 50 million PBLs from five MC patients with autoantibodies against the adenine nucleotide translocator (ANT), a myocardial autoantigen. The PBLs from three healthy blood donors were used as controls. After 60 days, human PBLs could be demonstrated in the peripheral blood of the SCID mice transfused with the PBLs of MC patients, representing up to 9.9% of the peripheral blood mononuclear cells. The transfused SCID mice sera showed human immunoglobulin levels of up to 3 mg/mL, both IgG and IgM. Autoantibodies against ANT were present in the mice receiving PBLs from MC patients but not from the control subjects. In addition, infiltrating human lymphocytes were present in the hearts of the SCID mice transfused with PBLs from MC patients. The presence of an ongoing autoimmune process in the SCID mice transfused with PBLs from MC patients is suggested by increased levels of soluble interleukin-2 receptor in the serum in contrast to SCID mice transfused with PBLs from healthy blood donors. We conclude that the autoimmune reactions seen in human MC can be transferred to SCID mice by the transfer of PBLs from MC patients. These findings stress the significance of autoimmune mechanisms in the pathogenesis of human MC.

This article has been cited by other articles:

				P. Blyszczuk, G. Kania, T. Dieterle, R. R. Marty, A. Valaperti, C. Berthonneche, T. Pedrazzini, C. T. Berger, S. Dirnhofer, C. M. Matter, et al. Myeloid Differentiation Factor-88/Interleukin-1 Signaling Controls Cardiac Fibrosis and Heart Failure Progression in Inflammatory Dilated Cardiomyopathy Circ. Res., October 23, 2009; 105(9): 912 - 920. [Abstract] [Full Text] [PDF]

				R. Dennert, H. J. Crijns, and S. Heymans Acute viral myocarditis Eur. Heart J., September 1, 2008; 29(17): 2073 - 2082. [Abstract] [Full Text] [PDF]

				G. Gao, J. Zhang, X. Si, J. Wong, C. Cheung, B. McManus, and H. Luo Proteasome inhibition attenuates coxsackievirus-induced myocardial damage in mice Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H401 - H408. [Abstract] [Full Text] [PDF]

				K. Shioji, Z. Yuan, T. Kita, and C. Kishimoto Immunoglobulin treatment suppressed adoptively transferred autoimmune myocarditis in severe combined immunodeficient mice Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2619 - H2625. [Abstract] [Full Text] [PDF]

				C. Kishimoto, Y. Hiraoka, N. Takamatsu, H. Takada, H. Kamiya, and H. Ochiai An in vivo model of autoimmune post-coxsackievirus B3 myocarditis in severe combined immunodeficiency mouse Cardiovasc Res, November 1, 2003; 60(2): 397 - 403. [Abstract] [Full Text] [PDF]

				J. W Mason Myocarditis and dilated cardiomyopathy: An inflammatory link Cardiovasc Res, October 15, 2003; 60(1): 5 - 10. [Abstract] [Full Text] [PDF]

				P. Liu, P. Lee, K. Fuse, and M. Nian Molecular pathophysiological mechanisms in virus infected host myocardium Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I37 - I41. [Abstract] [PDF]

				P. P. Liu and J. W. Mason Advances in the Understanding of Myocarditis Circulation, August 28, 2001; 104(9): 1076 - 1082. [Full Text] [PDF]

				A. Staudt, F. Schaper, V. Stangl, A. Plagemann, M. Bohm, K. Merkel, G. Wallukat, K. D. Wernecke, K. Stangl, G. Baumann, et al. Immunohistological Changes in Dilated Cardiomyopathy Induced by Immunoadsorption Therapy and Subsequent Immunoglobulin Substitution Circulation, June 5, 2001; 103(22): 2681 - 2686. [Abstract] [Full Text] [PDF]

				G.-H. Lee, C. Badorff, and K. U. Knowlton Dissociation of Sarcoglycans and the Dystrophin Carboxyl Terminus From the Sarcolemma in Enteroviral Cardiomyopathy Circ. Res., September 15, 2000; 87(6): 489 - 495. [Abstract] [Full Text] [PDF]

				S. B. Felix, A. Staudt, W. V. Dorffel, V. Stangl, K. Merkel, M. Pohl, W. D. Docke, S. Morgera, H. H. Neumayer, K. D. Wernecke, et al. Hemodynamic effects of immunoadsorption and subsequent immunoglobulin substitution in dilated cardiomyopathy: Three-month results from a randomized study J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1590 - 1598. [Abstract] [Full Text] [PDF]

				K. U. Knowlton and C. Badorff The Immune System in Viral Myocarditis : Maintaining the Balance Circ. Res., September 17, 1999; 85(6): 559 - 561. [Full Text] [PDF]

				H. Nakamura, T. Yamamura, S. Umemoto, S. Fukuta, T. Shioi, A. Matsumori, S. Sasayama, and M. Matsuzaki Autoimmune Response in Chronic Ongoing Myocarditis Demonstrated by Heterotopic Cardiac Transplantation in Mice Circulation, December 15, 1996; 94(12): 3348 - 3354. [Abstract] [Full Text]