IL-27 and TGF? mediated expansion of Th1 and adaptive regulatory T cells
expressing IL-10 correlates with bacterial burden and disease severity in
pulmonary tuberculosis
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Kumar NP
; Moideen K
; Banurekha VV
; Nair D
; Sridhar R
; Nutman TB
; Babu S
Immun Inflamm Dis
2015[Sep]; 3
(3
): 289-99
PMID26417443
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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(+), IFN?(+), T-bet(+)), Th2 (IL-10(+), IL-4(+),
GATA-3(+)), Th9 (IL-10(+), IL-9(+), IL-4(-)), Th17 (IL-10(+), IL-17(+), IFN?(-)),
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 TGF? play an important role in the regulation of IL-10(+) Th
cell subsets. Thus, active PTB is characterized by an IL-27 and TGF? 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.
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