title: Myocardial gene expression of T-bet, GATA-3, Ror-γt, FoxP3, and hallmark cytokines in chronic Chagas disease cardiomyopathy: an essentially unopposed TH1-type response.
abstract: BACKGROUND
  Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples.
  
  
  RESULTS
  Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-β and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4.
  
  
  CONCLUSIONS
  Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3(+)CTLA4(+) Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation.
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, 01246-903 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (iii), INCT, University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Luciana Gabriel
authors.initials: LG
authors.lastname: Nogueira
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Ronaldo Honorato Barros
authors.initials: RH
authors.lastname: Santos
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Alfredo Inácio
authors.initials: AI
authors.lastname: Fiorelli
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, 01246-903 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (iii), INCT, University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Eliane Conti
authors.initials: EC
authors.lastname: Mairena
authors.affiliation: Division of Pathology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Luiz Alberto
authors.initials: LA
authors.lastname: Benvenuti
authors.affiliation: Transplantation and Heart Failure Unit, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Edimar Alcides
authors.initials: EA
authors.lastname: Bocchi
authors.affiliation: Division of Surgery, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Noedir Antonio
authors.initials: NA
authors.lastname: Stolf
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, 01246-903 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (iii), INCT, University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, University of São Paulo School of Medicine, 01246-903 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (iii), INCT, University of São Paulo School of Medicine, 05403-000 São Paulo, SP, Brazil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D000328:Adult; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor