title: Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection.
abstract: Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (Tregs ) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN-γ and single IFN-γ-producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+) cells increased over time for both CD4(+) and CD8(+) T cells. The Treg subsets CD25(high) CD127(low) , CD25(high) CD147(++) and CD25(high) CD127(low) CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high) CD127(low) CD39(+) Tregs remained unchanged. The fraction of CD25(high) CD127(low) Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: S L
authors.initials: SL
authors.lastname: Feruglio
authors.forename: K
authors.initials: K
authors.lastname: Tonby
authors.forename: D
authors.initials: D
authors.lastname: Kvale
authors.forename: A M
authors.initials: AM
authors.lastname: Dyrhol-Riise
mesh_terms: D000217:Acyltransferases; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000378:metabolism; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D000995:Antitubercular Agents; D001426:Bacterial Proteins; D054316:Biomarkers, Pharmacological; C489634:CFP-10 protein (71-85), Mycobacterium tuberculosis; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010446:Peptide Fragments; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
keywords: T cells; Tregs; cytokines; treatment; tuberculosis