title: Cytokine production but lack of proliferation in peripheral blood mononuclear cells from chronic Chagas' disease cardiomyopathy patients in response to T. cruzi ribosomal P proteins.
abstract: BACKGROUND
  Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.
  
  
  RESULTS
  We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.
  
  
  CONCLUSIONS
  Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Silvia A
authors.initials: SA
authors.lastname: Longhi
authors.affiliation: Hospital General de Agudos J.M. Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Augusto
authors.initials: A
authors.lastname: Atienza
authors.affiliation: Hospital General de Agudos J. A. Fernández, Buenos Aires, Argentina.
authors.forename: Graciela
authors.initials: G
authors.lastname: Perez Prados
authors.affiliation: Torrey Pines Institute for Molecular Studies, San Diego, California, United States of America.
authors.forename: Alcinette
authors.initials: A
authors.lastname: Buying
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo Ugalde", Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Campus UNSAM, San Martín, Buenos Aires, Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Balouz
authors.affiliation: Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo Ugalde", Universidad Nacional de San Martín (UNSAM) - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Campus UNSAM, San Martín, Buenos Aires, Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Buscaglia
authors.affiliation: Torrey Pines Institute for Molecular Studies, Port St. Lucie, Florida, United States of America.
authors.forename: Radleigh
authors.initials: R
authors.lastname: Santos
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Tasso
authors.affiliation: Hospital General de Agudos J.M. Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bonato
authors.affiliation: Hospital General de Agudos J.M. Ramos Mejía, Buenos Aires, Argentina.
authors.forename: Pablo
authors.initials: P
authors.lastname: Chiale
authors.affiliation: Torrey Pines Institute for Molecular Studies, San Diego, California, United States of America.
authors.forename: Clemencia
authors.initials: C
authors.lastname: Pinilla
authors.affiliation: Torrey Pines Institute for Molecular Studies, San Diego, California, United States of America.
authors.forename: Valeria A
authors.initials: VA
authors.lastname: Judkowski
authors.affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI) - Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina; Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Gómez
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D002598:Chagas Cardiomyopathy / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D012269:Ribosomal Proteins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D016207:Cytokines; D010750:Phosphoproteins; D015800:Protozoan Proteins; D012269:Ribosomal Proteins; C031937:phosphoprotein P2, ribosomal; C084989:ribosomal PO protein, Trypanosoma cruzi