title: Regulatory T cells depress immune responses to protective antigens in active tuberculosis.
abstract: BACKGROUND
  Tuberculosis (TB) remains a leading cause of death, and the role of T-cell responses to control Mycobacterium tuberculosis infections is well recognized. Patients with latent TB infection develop strong IFN-gamma responses to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients with active TB do not.
  
  
  OBJECTIVE
  We investigated the mechanism of this difference and evaluated the possible involvement of regulatory T (Treg) cells and/or cytokines in the low HBHA T-cell responses of patients with active TB.
  
  
  METHODS
  The impact of anti-transforming growth factor (TGF)-beta and anti-IL-10 antibodies and of Treg cell depletion on the HBHA-induced IFN-gamma secretion was analyzed, and the Treg cell phenotype was characterized by flow cytometry.
  
  
  RESULTS
  Although the addition of anti-TGF-beta or anti-IL-10 antibodies had no effect on the HBHA-induced IFN-gamma secretion in patients with active TB, depletion of CD4(+)CD25(high)FOXP3(+) T lymphocytes resulted in the induction by HBHA of IFN-gamma concentrations that reached levels similar to those obtained for latent TB infection. No effect was noted on the early-secreted antigen target-6 or candidin T-cell responses.
  
  
  CONCLUSIONS
  Specific CD4(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Brussels, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hougardy
authors.forename: Sammy
authors.initials: S
authors.lastname: Place
authors.forename: Marc
authors.initials: M
authors.lastname: Hildebrand
authors.forename: Annie
authors.initials: A
authors.lastname: Drowart
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
authors.forename: Francoise
authors.initials: F
authors.lastname: Mascart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037102:Lectins / Q000276:immunology; D008212:Lymphocyte Depletion; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D037102:Lectins; C104578:heparin-binding hemagglutinin; D007371:Interferon-gamma