title: Increased frequencies of pulmonary regulatory T-cells in latent Mycobacterium tuberculosis infection.
abstract: Regulation of specific immune responses following exposure to Mycobacterium tuberculosis in humans and the role of regulatory T (Treg) cells in the immune control of latent infection with M. tuberculosis are incompletely understood. Latent infection was assayed by an interferon-γ release assay (IGRA) in healthcare workers regularly exposed to tuberculosis (TB) patients and in household TB contacts in Germany. Immunophenotypes of bronchoalveolar lavage (BAL) mononuclear cells and peripheral blood mononuclear cells (PBMCs) were analysed by fluorescence-activated cell sorting. All TB contacts with latent infection (n=15) had increased (p<0.0001) frequencies of CD4+ CD25+ CD127- Treg cells (median 2.12%, interquartile range (IQR) 1.63-3.01%) among BAL mononuclear cells compared with contacts (n=25) with negative IGRA results (median 0.68%, IQR 0.32-0.96%) No differences were seen when PBMC immunophenotypes of IGRA+ and IGRA- TB contacts were compared (IGRA+ median 9.6%, IQR 5.9-10.1%; IGRA- median 7.7%, IQR 4.6-11.3%; p=0.47). Five out of 25 contacts with negative blood IGRAs showed a positive IGRA from BAL cells, possibly indicating a limited local immune response. In Germany, latent infection with M. tuberculosis, as defined by a positive M. tuberculosis-specific IGRA response on cells from the peripheral blood, is characterised by an increased frequency of Treg cells in the BAL.
authors.affiliation: Clinical Infectious Diseases, Tuberculosis Center, Research Center Borstel, Borstel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herzmann
authors.forename: Martin
authors.initials: M
authors.lastname: Ernst
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Steffen
authors.initials: S
authors.lastname: Stenger
authors.forename: Jeroen
authors.initials: J
authors.lastname: Maertzdorf
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sotgiu
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D000328:Adult; D000368:Aged; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy / Q000379:methods; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005858:Germany; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000382:microbiology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000382:microbiology; D008168:Lung / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000382:microbiology*
chemical_list: D007371:Interferon-gamma