title: Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease.
abstract: The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy.
authors.affiliation: Department of Morphology Parasitology Graduate Program, Institute of Biological Sciences.
authors.forename: Lívia Silva Araújo
authors.initials: LS
authors.lastname: Passos
authors.affiliation: Department of Morphology.
authors.forename: Fernanda Nobre Amaral
authors.initials: FN
authors.lastname: Villani
authors.affiliation: Department of Morphology Parasitology Graduate Program, Institute of Biological Sciences.
authors.forename: Luísa Mourão Dias
authors.initials: LM
authors.lastname: Magalhães
authors.affiliation: Brazilian Research Institute for Scientific Advancement Instituto Nacional de Ciência e Tecnologia Doenças Tropicais Nucleo de Ensino e Pesquisa, Instituto Mario Penna.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Gollob
authors.affiliation: Instituto René Rachou, FIOCRUZ, Belo Horizonte, Brazil.
authors.forename: Lis Ribeiro do Vale
authors.initials: LR
authors.lastname: Antonelli
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais.
authors.forename: Maria Carmo Pereira
authors.initials: MC
authors.lastname: Nunes
authors.affiliation: Department of Morphology Parasitology Graduate Program, Institute of Biological Sciences Instituto Nacional de Ciência e Tecnologia Doenças Tropicais.
authors.forename: Walderez Ornelas
authors.initials: WO
authors.lastname: Dutra
mesh_terms: D000328:Adult; D055610:Antigens, CD1d / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014349:Trypanosoma cruzi / Q000276:immunology*; D055815:Young Adult
chemical_list: D055610:Antigens, CD1d; C526877:CD1D protein, human
keywords: CD1d; Chagas disease; Trypanosoma cruzi; cardiomyopathy; cytokines; double-negative T cells; immunoregulation; pathology