title: Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults.
abstract: BACKGROUND
  Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells.
  
  
  RESULTS
  To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4(+) T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4(+) T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4(+)TNF-α(+)-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4(+) T cells was evident in T. cruzi-infected children.
  
  
  CONCLUSIONS
  Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina ; Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Albareda
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: De Rissio
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Tomas
authors.affiliation: Hospital Fernandez, Buenos Aires, Argentina.
authors.forename: Alicia
authors.initials: A
authors.lastname: Serjan
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: María G
authors.initials: MG
authors.lastname: Alvarez
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Viotti
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fichera
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina.
authors.forename: Mónica I
authors.initials: MI
authors.lastname: Esteva
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Potente
authors.affiliation: Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Armenti
authors.affiliation: Center for Tropical and Emerging Global Diseases, Athens, Georgia, United States of America.
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
authors.affiliation: Instituto Nacional de Parasitología Dr. M. Fatala Chaben, Buenos Aires, Argentina ; Hospital Interzonal General de Agudos Eva Perón, Buenos Aires, Argentina.
authors.forename: Susana A
authors.initials: SA
authors.lastname: Laucella
mesh_terms: D000293:Adolescent; D000328:Adult; D023201:CD40 Ligand / Q000032:analysis; D014355:Chagas Disease / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma