title: Recombinant ESAT-6-CFP10 Fusion Protein Induction of Th1/Th2 Cytokines and FoxP3 Expressing Treg Cells in Pulmonary TB.
abstract: Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are Mycobacterium tuberculosis (Mtb)-specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors.
  
  
  
  Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC) were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest.
  
  
  
  The study confirmed that protective immune responses to rESAT-6-CFP10 are impaired in active TB but improved during treatment: circulating antigen-specific IL-4-producing T-cells were increased in untreated TB but declined by two weeks of treatment while the circulating antigen-specific IFN-γ producing T cells which showed a transient rise at one week of treatment, persisted at baseline levels at two months of treatment. In vitro T cell proliferation and IFN-γ production were reduced, while IL-4 and CD4(+)FoxP3(+)CD25(hi) cell expression were increased in response to rESAT-6-CFP10 fusion protein in untreated TB. These responses were reversed during early treatment of TB.
  
  
  
  These observations support further investigations into the possible utility of these parameters as markers of active disease and favourable treatment outcomes.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom ; Noguchi Memorial Institute for Medical Research (NMIMR), Accra, Ghana.
authors.forename: Dolly
authors.initials: D
authors.lastname: Jackson-Sillah
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Cliff
authors.forename: Gloria Ivy
authors.initials: GI
authors.lastname: Mensah
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dickson
authors.forename: Sandra
authors.initials: S
authors.lastname: Sowah
authors.forename: John K A
authors.initials: JK
authors.lastname: Tetteh
authors.forename: Kwasi K
authors.initials: KK
authors.lastname: Addo
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Graham
authors.initials: G
authors.lastname: Bothamley
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001500:BCG Vaccine; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005869:Ghana; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000276:immunology*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C113716:CFP17 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; C118437:negative elongation factor