title: CD4-CD8-αβ and γδ T cells display inflammatory and regulatory potentials during human tuberculosis.
abstract: T-cells play an important role controlling immunity against pathogens and therefore influence the outcome of human diseases. Although most T-lymphocytes co-express either CD4 or CD8, a smaller T-cell subset found the in the human peripheral blood that expresses the αβ or γδ T-cell-receptor (TCR) lacks the CD4 and CD8 co-receptors. These double negative (DN) T-cells have been shown to display important immunological functions in human diseases. To better understand the role of DN T-cells in human Mycobacterium tuberculosis, we have characterized their frequency, activation and cytokine profile in a well-defined group of tuberculosis patients, categorized as severe and non-severe based on their clinical status. Our data showed that whereas high frequency of αβ DN T-cells observed in M. tuberculosis-infected patients are associated with disease severity, decreased proportion of γδ DN T-cells are found in patients with severe tuberculosis. Together with activation of CD4(+) and CD8(+) T-cells, higher frequencies of both αβ and γδ DN T-cells from tuberculosis patients also express the chronic activation marker HLA-DR. However, the expression of CD69, an early activation marker, is selectively observed in DN T-cells. Interestingly, while αβ and γδ DN T-cells from patients with non-severe tuberculosis display a pro-inflammatory cytokine profile, characterized by enhanced IFN-γ, the γδ DN T-cells from patients with severe disease express a modulatory profile exemplified by enhanced interleukin-10 production. Overall, our findings suggest that αβ and γδ DN T-cell present disparate immunoregulatory potentials and seems to contribute to the development/maintenance of distinct clinical aspects of TB, as part of the complex immunological network triggered by the TB infection.
authors.affiliation: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Melina B
authors.initials: MB
authors.lastname: Pinheiro
authors.forename: Lis R
authors.initials: LR
authors.lastname: Antonelli
authors.forename: Renato
authors.initials: R
authors.lastname: Sathler-Avelar
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Vitelli-Avelar
authors.forename: Silvana
authors.initials: S
authors.lastname: Spindola-de-Miranda
authors.forename: Tânia M P D
authors.initials: TM
authors.lastname: Guimarães
authors.forename: Andrea
authors.initials: A
authors.lastname: Teixeira-Carvalho
authors.forename: Olindo A
authors.initials: OA
authors.lastname: Martins-Filho
authors.forename: Vicente P C P
authors.initials: VP
authors.lastname: Toledo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
chemical_list: D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016753:Interleukin-10