title: Enrichment of regulatory T-cells in blood of patients with multidrug-resistant tuberculosis.
abstract: OBJECTIVE
  To measure the percentage of regulatory T-cells (Treg) and the expression of signalling molecules in these cells from the peripheral blood of patients with multidrug-resistant tuberculosis (MDR-TB).
  
  
  METHODS
  Patients with drug-susceptible tuberculosis (S-TB), MDR-TB and healthy controls (HCs) were recruited into the study. Levels of CD4(+)CD25(+)Foxp3(+) Treg cells from peripheral blood, and programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible costimulatory (ICOS) molecule expression in the cells were measured using flow cytometry. Suppression mediated by Treg cells was assessed in carboxyfluorescein succinimidyl ester (CFSE) based suppression assays with autologous CD4(+)CD25(-) T-effector (Teff) cells.
  
  
  RESULTS
  Presence of Mycobacterium tuberculosis resulted in a higher proportion of Treg cells in S-TB patients than in HCs, and even higher levels in MDR-TB patients. Moreover, Treg cells in MDR-TB patients constitutively expressed high-level PD-1, CTLA-4 and ICOS. In addition, when cultured with activated CD4(+)CD25(-) Teff cells, Treg cells potently suppressed proliferation of Teff cells.
  
  
  CONCLUSIONS
  The high level of Treg cells found in the peripheral blood of tuberculosis patients may partly explain the poor immune response against M. tuberculosis, and could be a marker of MDR-TB.
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: W-P
authors.initials: WP
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Kong
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: R
authors.initials: R
authors.lastname: Min
authors.affiliation: Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, China.
authors.forename: C-M
authors.initials: CM
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: X-B
authors.initials: XB
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Lu
authors.affiliation: Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
authors.forename: X-H
authors.initials: XH
authors.lastname: Ji
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014376:Tuberculosis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D060889:Inducible T-Cell Co-Stimulator Protein; D053645:Interleukin-2 Receptor alpha Subunit