title: T Cell Responses and Regulation and the Impact of In Vitro IL-10 and TGF-β Modulation During Treatment of Active Tuberculosis.
abstract: 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/CD38 and PD-1/CD38 on both CD4+and CD8+T cells, while the fraction of CD4+CD25highCD127lowTregs (P = 0.017) and CD4+CD25highCD127lowCD147+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 CD4+CD25highCD127lowTregs 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.
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: S L
authors.identifier: http://orcid.org/0000-0002-5060-692X
authors.initials: SL
authors.lastname: Feruglio
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.|K. G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Kvale
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.|K. G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: A M
authors.initials: AM
authors.lastname: Dyrhol-Riise
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D017063:Outcome Assessment, Health Care; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D016212:Transforming Growth Factor beta; D016753:Interleukin-10