title: The frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® gold in-tube response in a prospective study of healthy indian adolescents.
abstract: BACKGROUND
  QuantiFERON-TB Gold In-Tube (QFT) is an IFNγ-release assay used in the diagnosis of Mycobacterium tuberculosis (MTB) infection. The risk of TB progression increases with the magnitude of the MTB-specific IFNγ-response. QFT reversion, also associated with low Tuberculin Skin Test responses, may therefore represent a transient immune response with control of M. tuberculosis infection. However, studies at the single cell level have suggested that the quality (polyfunctionality) of the T-cell response is more important than the quantity of cytokines produced.
  
  
  OBJECTIVE
  To explore the quality and/or magnitude of mycobacteria-specific T-cell responses associated with QFT reversion and persistent QFT-positivity.
  
  
  METHODS
  Multi-color flowcytometry on prospectively collected peripheral blood mononuclear cells was applied to assess mycobacteria-specific T-cell responses in 42 QFT positive Indian adolescents of whom 21 became QFT negative (reverters) within one year. Ten QFT consistent negatives were also included as controls.
  
  
  RESULTS
  There was no difference in the qualitative PPD-specific CD4+ T-cell response between QFT consistent positives and reverters. However, compared with QFT consistent positives, reverters displayed lower absolute frequencies of polyfunctional (IFNγ+IL2+TNFα+) CD4+ T-cells at baseline, which were further reduced to the point where they were not different to QFT negative controls one year later. Moreover, absolute frequencies of these cells correlated well with the magnitude of the QFT-response.
  
  
  CONCLUSIONS
  Whereas specific polyfunctional CD4+ T-cells have been suggested to protect against TB progression, our data do not support that higher relative or absolute frequencies of PPD-specific polyfunctional CD4+ T-cells in peripheral blood can explain the reduced risk of TB progression observed in QFT reverters. On the contrary, absolute frequencies of these cells correlated with the QFT-response, suggesting that this readout reflects antigenic load.
authors.affiliation: Centre for Immune Regulation and Department of Pathology, Oslo University Hospital - Rikshospitalet and the University of Oslo, Oslo, Norway.
authors.forename: Synne
authors.initials: S
authors.lastname: Jenum
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway, and Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Harleen M S
authors.initials: HM
authors.lastname: Grewal
authors.affiliation: Aeras, Rockville, Maryland, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Hokey
authors.affiliation: Division of Infectious Diseases, St. John's Research Institute, Bangalore, India.
authors.forename: John
authors.initials: J
authors.lastname: Kenneth
authors.affiliation: Physiology and Health and Humanities, St. John's Medical College and St. John's Research Institute, Bangalore, India.
authors.forename: Mario
authors.initials: M
authors.lastname: Vaz
authors.affiliation: GlaxoSmithKline Pharma, Vaccines, Copenhagen, Denmark.
authors.forename: Timothy Mark
authors.initials: TM
authors.lastname: Doherty
authors.affiliation: Centre for Immune Regulation and Department of Pathology, Oslo University Hospital - Rikshospitalet and the University of Oslo, Oslo, Norway.
authors.forename: Frode Lars
authors.initials: FL
authors.lastname: Jahnsen
mesh_terms: D000293:Adolescent; D044466:Asian People; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D006046:Gold / Q000737:chemistry; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D011933:Reagent Kits, Diagnostic; D014409:Tumor Necrosis Factor-alpha; D006046:Gold; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens