Role of Trypanosoma cruzi Autoreactive T Cells in the Generation of Cardiac Pathology

Abstract:  Chagas disease, caused by Trypanosoma cruzi, affects several million people in Central and South America. About 30% of chronic patients develop cardiomyopathy probably caused by parasite persistence and/or autoimmunity. While several cross‐reactive antibodies generated during mammal T. cruzi infection have been described, very few cross‐reactive T cells have been identified. We performed adoptive transfer experiments of T cells isolated from chronically infected mice. The results showed the generation of cardiac pathology in the absence of parasites. We also transferred cross‐reactive SAPA‐specific T cells and observed unspecific alterations in heart repolarization, cardiac inflammatory infiltration, and tissue damage.

[1]  C. Alonso,et al.  The genetic immunization with paraflagellar rod protein-2 fused to the HSP70 confers protection against late Trypanosoma cruzi infection. , 2006, Vaccine.

[2]  R. Tarleton,et al.  Endogenous CD4+ CD25+ Regulatory T Cells Have a Limited Role in the Control of Trypanosoma cruzi Infection in Mice , 2006, Infection and Immunity.

[3]  M. Fresno,et al.  The efficacy of photochemical treatment with methylene blue and light for the reduction of Trypanosoma cruzi in infected plasma , 2006, Vox sanguinis.

[4]  R. Tarleton,et al.  Limited Role for CD4+ T-Cell Help in the Initial Priming of Trypanosoma cruzi-Specific CD8+ T Cells , 2006, Infection and Immunity.

[5]  R. Gazzinelli,et al.  Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase. , 2006, Human gene therapy.

[6]  Alessandro Sette,et al.  CD8+ T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes , 2006, PLoS pathogens.

[7]  J. Urbina,et al.  Cytoskeleton reassembly in cardiomyocytes infected by Trypanosoma cruzi is triggered by treatment with ergosterol biosynthesis inhibitors. , 2006, International journal of antimicrobial agents.

[8]  R. Tarleton,et al.  Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients. , 2006, International immunology.

[9]  D. Engman,et al.  Further thoughts on where we stand on the autoimmunity hypothesis of Chagas disease. , 2006, Trends in parasitology.

[10]  J. Kalil,et al.  Induction of cardiac autoimmunity in Chagas heart disease: A case for molecular mimicry , 2006, Autoimmunity.

[11]  F. Kierszenbaum Where do we stand on the autoimmunity hypothesis of Chagas disease? , 2005, Trends in parasitology.

[12]  Y. Takashima,et al.  Immune Responses against a Single CD8+-T-Cell Epitope Induced by Virus Vector Vaccination Can Successfully Control Trypanosoma cruzi Infection , 2005, Infection and Immunity.

[13]  M. Toldo,et al.  Trypanosoma cruzi: the effects of dehydroepiandrosterone (DHEA) treatment during experimental infection. , 2005, Acta tropica.

[14]  A. Gruber,et al.  T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13 protein. , 2005, Microbes and infection.

[15]  B. Haas,et al.  The Genome Sequence of Trypanosoma cruzi, Etiologic Agent of Chagas Disease , 2005, Science.

[16]  L. Juliano,et al.  T-cell molecular mimicry in Chagas disease: identification and partial structural analysis of multiple cross-reactive epitopes between Trypanosoma cruzi B13 and cardiac myosin heavy chain. , 2005, Journal of autoimmunity.

[17]  R. Tarleton,et al.  Generation, specificity, and function of CD8+ T cells in Trypanosoma cruzi infection , 2004, Immunological reviews.

[18]  R. Gazzinelli,et al.  Protective immunity against trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase. , 2004, Human gene therapy.

[19]  M. L. Lo Presti,et al.  Thioridazine treatment prevents cardiopathy in Trypanosoma cruzi infected mice. , 2004, International journal of antimicrobial agents.

[20]  R. Tarleton,et al.  Frequency of interferon- gamma -producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease. , 2004, The Journal of infectious diseases.

[21]  E. Chiari,et al.  Use of the Trypanosoma cruzi Recombinant Complement Regulatory Protein To Evaluate Therapeutic Efficacy following Treatment of Chronic Chagasic Patients , 2004, Journal of Clinical Microbiology.

[22]  D. Engman,et al.  Myosin Autoimmunity Is Not Essential for Cardiac Inflammation in Acute Chagas’ Disease 1 , 2003, The Journal of Immunology.

[23]  R. Tarleton Chagas disease: a role for autoimmunity? , 2003, Trends in parasitology.

[24]  F. Kierszenbaum Views on the autoimmunity hypothesis for Chagas disease pathogenesis. , 2003, FEMS immunology and medical microbiology.

[25]  R. Tarleton,et al.  Cutting Edge: Dysfunctional CD8+ T Cells Reside in Nonlymphoid Tissues During Chronic Trypanosoma cruzi Infection 1 , 2003, The Journal of Immunology.

[26]  R. Ribeiro‐dos‐Santos,et al.  Experimental chronic Chagas' disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens. , 2002, Journal of autoimmunity.

[27]  D. Engman,et al.  Pathogenesis of Chagas heart disease: role of autoimmunity. , 2002, Acta tropica.

[28]  R. Ribeiro‐dos‐Santos,et al.  The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet. , 2001, Anais da Academia Brasileira de Ciencias.

[29]  A. Fournet,et al.  Experimental treatment of chronic Trypanosoma cruzi infection in mice with 2‐n‐propylquinoline , 2001, Phytotherapy research : PTR.

[30]  M. Fresno,et al.  Antibodies to an Epitope from the Cha Human Autoantigen Are Markers of Chagas' Disease , 2001, Clinical Diagnostic Laboratory Immunology.

[31]  A Prata,et al.  Clinical and epidemiological aspects of Chagas disease. , 2001, The Lancet. Infectious diseases.

[32]  M. Rodrigues,et al.  DNA Sequences Encoding CD4+ and CD8+T-Cell Epitopes Are Important for Efficient Protective Immunity Induced by DNA Vaccination with a Trypanosoma cruziGene , 2001, Infection and Immunity.

[33]  D. Engman,et al.  Cardiac Myosin Autoimmunity in Acute Chagas' Heart Disease , 2001, Infection and Immunity.

[34]  C. Benoist,et al.  Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry? , 2001, Nature Immunology.

[35]  C. Mady,et al.  Chronic Chagas' disease cardiomyopathy patients display an increased IFN-gamma response to Trypanosoma cruzi infection. , 2001, Journal of autoimmunity.

[36]  D. Engman,et al.  Autoimmunity in Chagas heart disease. , 2001, International journal for parasitology.

[37]  R. Tarleton Parasite persistence in the aetiology of Chagas disease. , 2001, International journal for parasitology.

[38]  M. Fresno,et al.  Dominant T- and B-cell epitopes in an autoantigen linked to Chagas' disease. , 2001, The Journal of clinical investigation.

[39]  R. Ribeiro‐dos‐Santos,et al.  A heart‐specific CD4+ T‐cell line obtained from a chronic chagasic mouse induces carditis in heart‐immunized mice and rejection of normal heart transplants in the absence of Trypanosoma cruzi , 2001, Parasite immunology.

[40]  F. Kierszenbaum Chagas’ Disease and the Autoimmunity Hypothesis , 1999, Clinical Microbiology Reviews.

[41]  R. Tarleton,et al.  Chagas disease etiology: autoimmunity or parasite persistence? , 1999, Parasitology today.

[42]  S. Wendel Transfusion-transmitted Chagas' disease. , 1998, Current opinion in hematology.

[43]  B. Burleigh,et al.  Signaling and host cell invasion by Trypanosoma cruzi. , 1998, Current opinion in microbiology.

[44]  J. Kalil,et al.  Molecular mimicry between cardiac myosin and Trypanosoma cruzi antigen B13: identification of a B13-driven human T cell clone that recognizes cardiac myosin. , 1997, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[45]  R. Tarleton,et al.  "Autoimmune rejection" of neonatal heart transplants in experimental Chagas disease is a parasite-specific response to infected host tissue. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Levin In chronic Chagas heart disease, don't forget the parasite. , 1996, Parasitology today.

[47]  L. Guilherme,et al.  Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient. , 1996, The Journal of clinical investigation.

[48]  A. Gruber,et al.  Autoimmunity in Chagas disease cardiopathy: biological relevance of a cardiac myosin-specific epitope crossreactive to an immunodominant Trypanosoma cruzi antigen. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[49]  M. Rossi,et al.  Anti-CD4 abrogates rejection and reestablishes long-term tolerance to syngeneic newborn hearts grafted in mice chronically infected with Trypanosoma cruzi , 1992, The Journal of experimental medicine.

[50]  H. Eisen,et al.  Mimicry in Trypanosoma cruzi: fantasy and reality. , 1991, Current opinion in immunology.

[51]  L. Kirchhoff Is Trypanosoma cruzi a new threat to our blood supply? , 1989, Annals of internal medicine.

[52]  T. McCormick,et al.  Trypanosoma cruzi: cross-reactive anti-heart autoantibodies produced during infection in mice. , 1989, Experimental parasitology.

[53]  R. Isturiz,et al.  Chagas Disease , 2021, Neglected Tropical Diseases.

[54]  C. A. Santos-Buch,et al.  Autoimmune myocarditis induced by Trypanosoma cruzi. , 1985, Circulation.

[55]  O. Bustuoabad,et al.  Experimental myocarditis induced in Swiss mice by homologous heart immunization resembles chronic experimental Chagas' heart disease. , 1984, Clinical immunology and immunopathology.

[56]  T. Jessell,et al.  A monoclonal antibody defining antigenic determinants on subpopulations of mammalian neurones and Trypanosoma cruzi parasites , 1982, Nature.

[57]  E. Khoury,et al.  CHAGAS' DISEASE AND AUTOIMMUNITY , 1980, The Lancet.

[58]  A. Szarfman,et al.  Chagasic Cardiopathy: Antibodies Reacting with Plasma Membrane of Striated Muscle and Endothelial Cells , 1974, Circulation.

[59]  A. Teixeira,et al.  THE IMMUNOLOGY OF EXPERIMENTAL CHAGAS' DISEASE , 1974, The Journal of experimental medicine.

[60]  A. Szarfman,et al.  Chagasic Cardiopathy: Demonstration of a Serum Gamma Globulin Factor Which Reacts with Endocardium and Vascular Structures , 1974, Circulation.

[61]  F. Laranja,et al.  Chagas' Disease: A Clinical, Epidemiologic, and Pathologic Study , 1956, Circulation.

[62]  S. Mazza La enfermedad de Chagas en la Republica Argentina , 1949 .

[63]  Carlos Chagas,et al.  Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem , 1909 .

[64]  R. Tarleton,et al.  Endogenous CD 4 + CD 25 + Regulatory T Cells Have Limited Role in Control of Trypanosoma cruzi Infection in Mice , 2006 .

[65]  M. Fresno,et al.  Trypanosoma cruzi-induced molecular mimicry and Chagas' disease. , 2005, Current topics in microbiology and immunology.

[66]  C. Alonso-Vega,et al.  [Integral treatment of congenital Chagas disease: the Bolivian experience ]. , 2005, Revista da Sociedade Brasileira de Medicina Tropical.

[67]  J. Altcheh,et al.  [Congenital Chagas disease: experience in the Hospital de Niños, Ricardo Gutiérrez, Buenos Aires, Argentina]. , 2005, Revista da Sociedade Brasileira de Medicina Tropical.

[68]  M. Fresno,et al.  Etiology of Chagas disease myocarditis: autoimmunity, parasite persistence, or both? , 2003, Trends in parasitology.

[69]  Á. Moncayo Progress towards interruption of transmission of Chagas disease. , 1999, Memorias do Instituto Oswaldo Cruz.

[70]  G. Takle,et al.  Autoimmunity and Chagas' disease. , 1989, Current topics in microbiology and immunology.

[71]  A. M. Acosta Autoimmunity in Chagas' disease. , 1987, The Journal of parasitology.