title: Trypanosoma cruzi-induced activation of functionally distinct αβ and γδ CD4- CD8- T cells in individuals with polar forms of Chagas' disease.
abstract: CD4(-) CD8(-) (double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express γδ or αβ T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while αβ DN T cells serve primarily to express inflammatory cytokines, γδ DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruzi experimental infection. In this work, we sought to investigate whether αβ or γδ DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitro infection with T. cruzi leads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while αβ DN T cells primarily produce inflammatory cytokines in both forms of the disease, γδ DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing γδ DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for αβ and γδ DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.
authors.affiliation: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernanda Nobre Amaral
authors.initials: FN
authors.lastname: Villani
authors.forename: Manoel Otávio da Costa
authors.initials: MO
authors.lastname: Rocha
authors.forename: Maria do Carmo Pereira
authors.initials: Mdo C
authors.lastname: Nunes
authors.forename: Lis Ribeiro do Valle
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Luisa Mourão Dias
authors.initials: LM
authors.lastname: Magalhães
authors.forename: Janete Soares Coelho
authors.initials: JS
authors.lastname: dos Santos
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Gollob
authors.forename: Walderez O
authors.initials: WO
authors.lastname: Dutra
mesh_terms: D000328:Adult; D000368:Aged; D014355:Chagas Disease / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000502:physiology*; D055815:Young Adult
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10