title: CD4(+) CD25(high) forkhead box protein 3(+) regulatory T lymphocytes suppress interferon-γ and CD107 expression in CD4(+) and CD8(+) T cells from tuberculous pleural effusions.
abstract: Tuberculous pleural effusion is characterized by a T helper type 1 (Th1) profile, but an excessive Th1 response may also cause tissue damage that might be controlled by regulatory mechanisms. In the current study we investigated the role of regulatory T cells (Treg ) in the modulation of Th1 responses in patients with tuberculous (TB) pleurisy. Using flow cytometry we evaluated the proportion of Treg (CD4(+) CD25(high) forkhead box protein 3(+) ), interferon (IFN)-γ and interleukin (IL)-10 expression and CD107 degranulation in peripheral blood (PB) and pleural fluid (PF) from patients with TB pleurisy. We demonstrated that the proportion of CD4(+) CD25(+) , CD4(+) CD25(high) FoxP3(+) and CD8(+) CD25(+) cells were increased in PF compared to PB samples. Mycobacterium tuberculosis stimulation increased the proportion of CD4(+) CD25(low/neg) IL-10(+) in PB and CD4(+) CD25(low/neg) IFN-γ(+) in PF; meanwhile, CD25(high) mainly expressed IL-10 in both compartments. A high proportion of CD4(+) CD107(+) and CD8(+) CD107(+) cells was observed in PF. Treg depletion enhanced the in-vitro M. tuberculosis-induced IFN-γ and CD4(+) and CD8(+) degranulation responses and decreased CD4(+) IL-10(+) cells in PF. Our results demonstrated that in TB pleurisy Treg cells effectively inhibit not only IFN-γ expression but also the ability of CD4(+) and CD8(+) cells to degranulate in response to M. tuberculosis.
authors.affiliation: IMEX-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Geffner
authors.forename: J I
authors.initials: JI
authors.lastname: Basile
authors.forename: N
authors.initials: N
authors.lastname: Yokobori
authors.forename: C
authors.initials: C
authors.lastname: Sabio Y García
authors.forename: R
authors.initials: R
authors.lastname: Musella
authors.forename: J
authors.initials: J
authors.lastname: Castagnino
authors.forename: M C
authors.initials: MC
authors.lastname: Sasiain
authors.forename: S
authors.initials: S
authors.lastname: de la Barrera
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010996:Pleural Effusion / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000276:immunology*; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D052118:Lysosomal-Associated Membrane Protein 1; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD107; T regulatory; pleural effusions; tuberculosis