HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fedoseyeva, E. V. Articles by Benichou, G. Search for Related Content PubMed PubMed Citation Articles by Fedoseyeva, E. V. Articles by Benichou, G. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Autoimmune Diseases Cardiomyopathy Heart Transplantation

De Novo Autoimmunity to Cardiac Myosin After Heart Transplantation and Its Contribution to the Rejection Process¹

Eugenia V. Fedoseyeva^2,*, Feng Zhang, Patricia L. Orr^*, David Levin, Harry J. Buncke and Gilles Benichou^2,3,*

^* Department of Surgery and Immunogenetics and Transplantation Laboratory, Microsurgical Laboratory, and Department of Pathology, Davies Medical Center, University of California School of Medicine, San Francisco, CA 94114.

Allograft rejection is initiated by an immune response to donor MHC proteins. We recently reported that this response can result in breakdown of immune tolerance to a recipient self Ag. However, the contribution of this autoimmune response to graft rejection has yet to be determined. Here, we found that after mouse allogeneic heart transplantation, de novo CD4⁺ T cell and B cell autoimmune response to cardiac myosin (CM), a major contractile protein of cardiac muscle, is elicited in recipients. Importantly, CM is the autoantigen that causes autoimmune myocarditis, a heart autoimmune disease whose histopathological features resemble those observed in rejected cardiac transplants. Furthermore, T cell responses directed to CM peptide myhc 334–352, a known myocarditogenic determinant, were detected in heart-transplanted mice. No responses to CM were observed in mice that had received an allogeneic skin graft or a syngeneic heart transplant, demonstrating that this response is tissue specific and that allogeneic response is necessary to break tolerance to CM. Next, we showed that sensitization of recipient mice with CM markedly accelerates the rejection of allogeneic heart. Therefore, posttransplant autoimmune response to CM is relevant to the rejection process. We conclude that transplantation-induced autoimmune response to CM represents a new mechanism that may play a significant role in cardiac transplant rejection.

This article has been cited by other articles:

				T. S. Win, S. Rehakova, M. C. Negus, K. Saeb-Parsy, M. Goddard, T. M. Conlon, E. M. Bolton, J. A. Bradley, and G. J. Pettigrew Donor CD4 T Cells Contribute to Cardiac Allograft Vasculopathy by Providing Help for Autoantibody Production Circ Heart Fail, July 1, 2009; 2(4): 361 - 369. [Abstract] [Full Text] [PDF]

				N. Fukami, S. Ramachandran, D. Saini, M. Walter, W. Chapman, G. A. Patterson, and T. Mohanakumar Antibodies to MHC Class I Induce Autoimmunity: Role in the Pathogenesis of Chronic Rejection J. Immunol., January 1, 2009; 182(1): 309 - 318. [Abstract] [Full Text] [PDF]

				T. A. Goers, S. Ramachandran, A. Aloush, E. Trulock, G. A. Patterson, and T. Mohanakumar De Novo Production of K-{alpha}1 Tubulin-Specific Antibodies: Role in Chronic Lung Allograft Rejection J. Immunol., April 1, 2008; 180(7): 4487 - 4494. [Abstract] [Full Text] [PDF]

				B. Mahesh, H.-S. Leong, A. McCormack, P. Sarathchandra, A. Holder, and M. L. Rose Autoantibodies to Vimentin Cause Accelerated Rejection of Cardiac Allografts Am. J. Pathol., April 1, 2007; 170(4): 1415 - 1427. [Abstract] [Full Text] [PDF]

				J. Wehner, C. N. Morrell, T. Reynolds, E. R. Rodriguez, and W. M. Baldwin III Antibody and Complement in Transplant Vasculopathy Circ. Res., February 2, 2007; 100(2): 191 - 203. [Abstract] [Full Text] [PDF]

				J. S. Leon, M. D. Daniels, K. M. Toriello, K. Wang, and D. M. Engman A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization with Trypanosoma cruzi Proteins Infect. Immun., June 1, 2004; 72(6): 3410 - 3417. [Abstract] [Full Text] [PDF]

				T. L. Sumpter and D. S. Wilkes Role of autoimmunity in organ allograft rejection: a focus on immunity to type V collagen in the pathogenesis of lung transplant rejection Am J Physiol Lung Cell Mol Physiol, June 1, 2004; 286(6): L1129 - L1139. [Abstract] [Full Text] [PDF]

				J. S. Leon, K. Wang, and D. M. Engman Myosin Autoimmunity Is Not Essential for Cardiac Inflammation in Acute Chagas' Disease J. Immunol., October 15, 2003; 171(8): 4271 - 4277. [Abstract] [Full Text] [PDF]

				P. Hamrah, S. O. Huq, Y. Liu, Q. Zhang, and M. R. Dana Corneal immunity is mediated by heterogeneous population of antigen-presenting cells J. Leukoc. Biol., August 1, 2003; 74(2): 172 - 178. [Abstract] [Full Text] [PDF]

				Z. E. Holzknecht, K. L. Kuypers, T. B. Plummer, J. Williams, M. Bustos, G. J. Gores, G. J. Brunn, and J. L. Platt Apoptosis and Cellular Activation in the Pathogenesis of Acute Vascular Rejection Circ. Res., December 13, 2002; 91(12): 1135 - 1141. [Abstract] [Full Text] [PDF]

				E. V. Fedoseyeva, K. Kishimoto, H. K. Rolls, B. M.-W. Illigens, V. M. Dong, A. Valujskikh, P. S. Heeger, M. H. Sayegh, and G. Benichou Modulation of Tissue-Specific Immune Response to Cardiac Myosin Can Prolong Survival of Allogeneic Heart Transplants J. Immunol., August 1, 2002; 169(3): 1168 - 1174. [Abstract] [Full Text] [PDF]

				M. A. Haque, T. Mizobuchi, K. Yasufuku, T. Fujisawa, R. R. Brutkiewicz, Y. Zheng, K. Woods, G. N. Smith, O. W. Cummings, K. M. Heidler, et al. Evidence for Immune Responses to a Self-Antigen in Lung Transplantation: Role of Type V Collagen-Specific T Cells in the Pathogenesis of Lung Allograft Rejection J. Immunol., August 1, 2002; 169(3): 1542 - 1549. [Abstract] [Full Text] [PDF]

				Y. Liu, P. Hamrah, Q. Zhang, A. W. Taylor, and M. R. Dana Draining Lymph Nodes of Corneal Transplant Hosts Exhibit Evidence for Donor Major Histocompatibility Complex (MHC) Class II-positive Dendritic Cells Derived from MHC Class II-negative Grafts J. Exp. Med., January 22, 2002; 195(2): 259 - 268. [Abstract] [Full Text] [PDF]

				E. Lovegrove, G. J. Pettigrew, E. M. Bolton, and J. A. Bradley Epitope Mapping of the Indirect T Cell Response to Allogeneic Class I MHC: Sequences Shared by Donor and Recipient MHC May Prime T Cells That Provide Help for Alloantibody Production J. Immunol., October 15, 2001; 167(8): 4338 - 4344. [Abstract] [Full Text] [PDF]

				J. S. Leon, L. M. Godsel, K. Wang, and D. M. Engman Cardiac Myosin Autoimmunity in Acute Chagas' Heart Disease Infect. Immun., September 1, 2001; 69(9): 5643 - 5649. [Abstract] [Full Text] [PDF]

				K. Yasufuku, K. M. Heidler, P. W. O'Donnell, G. N. Smith Jr., O. W. Cummings, B. H. Foresman, T. Fujisawa, and D. S. Wilkes Oral Tolerance Induction by Type V Collagen Downregulates Lung Allograft Rejection Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 26 - 34. [Abstract] [Full Text] [PDF]

				K. Portugal, I. Dozmorov, I. Sidorov, I. Marrero, J. A. Fonseca, M. Spadafora-Ferreira, J. Kalil, and V. Coelho Renal transplant patients show variations in their self-reactive repertoires: a serial study Int. Immunol., June 1, 2001; 13(6): 747 - 755. [Abstract] [Full Text] [PDF]

				K. Gagne, S. Brouard, M. Giral, F. Sebille, A. Moreau, M. Guillet, J.-D. Bignon, B.-M. Imbert, M.-C. Cuturi, and J.-P. Soulillou Highly Altered V{beta} Repertoire of T Cells Infiltrating Long-Term Rejected Kidney Allografts J. Immunol., February 1, 2000; 164(3): 1553 - 1563. [Abstract] [Full Text] [PDF]