IL-27 and TGFß mediated expansion of Th1 and adaptive regulatory T cells expressing IL-10 correlates with bacterial burden and disease severity in pulmonary tuberculosis.

Kumar, N.P.; Moideen, K.; Banurekha, V.V.; Dina, N.; Sridhar, R.; Nutman, T.B.; Babu, S .

Immune Inflammatory Diseases; 2015; 3; 289-299.   

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 + , IFN g + , T-bet + ), Th2 (IL-10 + , IL-4 + GATA-3 + ), Th9 (IL-10 + , IL-9 + , IL-4 ¯ ), Th17 (IL-10 + , IL-17 + , IFN g ¯ ), 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 b play an important role in the regulation of IL-10 + Th cell subsets. Thus, active PTB is characterized by an IL-27 and TGF b 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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