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T Cell Responses and Regulation and the Impact of In Vitro IL ‐10 and TGF ‐ β Modulation During Treatment of Active Tuberculosis
Author(s) -
Feruglio S. L.,
Kvale D.,
DyrholRiise A. M.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12511
Subject(s) - flow cytometry , t cell , immunology , cytokine , immune system , in vitro , mycobacterium tuberculosis , biology , cell , cell growth , antigen , microbiology and biotechnology , tuberculosis , medicine , biochemistry , pathology
Mycobacterium tuberculosis ( Mtb ) is particularly challenging for the immune system being an intracellular pathogen, and a variety of T cell subpopulations are activated by the host defence mechanism. In this study, we investigated T cell responses and regulation in active TB patients with drug‐sensitive Mtb (N = 18) during 24 weeks of efficient anti‐ TB therapy. T cell activation, differentiation, regulatory T cell (Treg) subsets, Mtb ‐induced T cell proliferation and in vitro IL ‐10 and TGF ‐ β modulation were analysed by flow cytometry at baseline and after 8 and 24 weeks of therapy, while soluble cytokines in culture supernatants were analysed by a 9‐plex Luminex assay. Successful treatment resulted in significantly reduced co‐expression of HLA ‐ DR / CD 38 and PD ‐1/ CD 38 on both CD 4 + and CD 8 + T cells, while the fraction of CD 4 + CD 25 high CD 127 low Tregs ( P = 0.017) and CD 4 + CD 25 high CD 127 low CD 147 + Tregs ( P = 0.029) showed significant transient increase at week 8. In vitro blockade of IL ‐10/ TGF ‐ β upon Mtb antigen stimulation significantly lowered the fraction of ESAT ‐6‐specific CD 4 + CD 25 high CD 127 low Tregs at baseline ( P = 0.047), while T cell proliferation and cytokine production were unaffected. Phenotypical and Mtb ‐specific T cell signatures may serve as markers of effective therapy, while the IL ‐10/ TGF ‐ β pathway could be a target for early inhibition to facilitate Mtb clearance. However, larger clinical studies are needed for verification before concluding.