T Cell Responses and Regulation and the Impact of In VitroIL-10 and TGF-[beta] Modulation During Treatment of Active Tuberculosis

• Published in: Scandinavian journal of immunology 2017-02, Vol.85 (2), p.138
• Main Authors: Feruglio, S L, Kvale, D, Dyrhol-Riise, A M
• Format: Article
• Language: English
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12511

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 vitroIL-10 and TGF-[beta] 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/CD38 and PD-1/CD38 on both CD4+ and CD8+ T cells, while the fraction of CD4+CD25highCD127low Tregs (P = 0.017) and CD4+CD25highCD127low CD147+ Tregs (P = 0.029) showed significant transient increase at week 8. In vitro blockade of IL-10/TGF-[beta] upon Mtb antigen stimulation significantly lowered the fraction of ESAT-6-specific CD4+CD25highCD127low 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-[beta] pathway could be a target for early inhibition to facilitate Mtb clearance. However, larger clinical studies are needed for verification before concluding.