title: Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis.
abstract: BACKGROUND
  The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20-30% of infected individuals but not until 10-20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis.
  
  
  RESULTS
  The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3(+), CD4(+), CD8(+), CD45RO(+)) with a low grade of differentiation (CD27(+), CD57(-), CD45RA(-), PD(-)1(-)). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3(+) cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3(+) T cells, assessed by Ki67 staining, was found.
  
  
  CONCLUSIONS
  The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection.
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chabén", Buenos Aires, Argentina.
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Argüello
authors.affiliation: Departamento de Patología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vigliano
authors.affiliation: Departamento de Patología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Cabeza-Meckert
authors.affiliation: Servicio de Cardiología, Sección de Chagas, Hospital Interzonal General de Agudos "Eva Perón", San Martín, Buenos Aires, Argentina.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Viotti
authors.affiliation: Laboratorio de Eco-Epidemiología de la enfermedad de Chagas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Fernando
authors.initials: F
authors.lastname: Garelli
authors.affiliation: Departamento de Trasplante Intratorácico. Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Liliana E
authors.initials: LE
authors.lastname: Favaloro
authors.affiliation: Departamento de Trasplante Intratorácico. Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Roberto R
authors.initials: RR
authors.lastname: Favaloro
authors.affiliation: Departamento de Patología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
authors.forename: Rubén
authors.initials: R
authors.lastname: Laguens
authors.affiliation: Instituto Nacional de Parasitología "Dr. Mario Fatala Chabén", Buenos Aires, Argentina; Servicio de Cardiología, Sección de Chagas, Hospital Interzonal General de Agudos "Eva Perón", San Martín, Buenos Aires, Argentina.
authors.forename: Susana A
authors.initials: SA
authors.lastname: Laucella
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D049109:Cell Proliferation; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen