title: IL-27 and TGFβ mediated expansion of Th1 and adaptive regulatory T cells expressing IL-10 correlates with bacterial burden and disease severity in pulmonary tuberculosis.
abstract: CD4(+) T cell expression of IL-10 is an important mechanism controlling immunity to tuberculosis (TB). To identify the CD4(+) T cell subsets producing IL-10 in human TB, we enumerated the frequencies of IL-10 expressing CD4(+) T cell subsets following TB-antigen stimulation of cells from individuals with pulmonary (PTB) and latent TB (LTB). We first demonstrate that TB antigens induce an expansion of IL-10 expressing Th1 (IL-10(+), IFNγ(+), T-bet(+)), Th2 (IL-10(+), IL-4(+), GATA-3(+)), Th9 (IL-10(+), IL-9(+), IL-4(-)), Th17 (IL-10(+), IL-17(+), IFNγ(-)), and natural and adaptive regulatory T cells [nTregs; IL-10(+), CD4(+), CD25(+), Foxp3(+) and aTregs; IL-10 single(+), CD4(+), CD25(-), Foxp3(-)] in PTB and LTB individuals, with frequencies being significantly higher in the former. However, only Th1 cells and adaptive Tregs expressing IL-10 exhibit a positive relationship with bacterial burdens and extent of disease in PTB. Finally, we show that IL-27 and TGFβ play an important role in the regulation of IL-10(+) Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGFβ mediated expansion of IL-10 expressing CD4(+) T cell subsets, with IL-10(+) Th1 and IL-10(+) aTreg cells playing a potentially pivotal role in the pathogenesis of active disease.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research Chennai, India.
authors.forename: Nathella P
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: National Institutes of Health-International Center for Excellence in Research Chennai, India.
authors.forename: Kadar
authors.initials: K
authors.lastname: Moideen
authors.affiliation: National Institute for Research in Tuberculosis Chennai, India.
authors.forename: Vaithilingam V
authors.initials: VV
authors.lastname: Banurekha
authors.affiliation: National Institute for Research in Tuberculosis Chennai, India.
authors.forename: Dina
authors.initials: D
authors.lastname: Nair
authors.affiliation: Government Stanley Medical Hospital Chennai, India.
authors.forename: Rathinam
authors.initials: R
authors.lastname: Sridhar
authors.affiliation: Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.affiliation: National Institutes of Health-International Center for Excellence in Research Chennai, India ; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland, USA.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
keywords: Cytokines; IL-10; T cells; regulation; tuberculosis