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

Immunity, Inflammation and Disease

Nathella P. Kumar⁴  Kadar Moideen⁴  Vaithilingam V. Banurekha²  Dina Nair²  Rathinam Sridhar¹  Thomas B. Nutman³ 

[1] Government Stanley Medical Hospital, Chennai, India;National Institute for Research in Tuberculosis, Chennai, India;Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA;National Institutes of Health—International Center for Excellence in Research, Chennai, India

关键词: Cytokines;    IL‐10;    regulation;    T cells;    tuberculosis;   

DOI  :  10.1002/iid3.68

来源: Wiley

【 摘 要 】

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.

【 授权许可】

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© 2015 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

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