title: FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis.
abstract: BACKGROUND
  The inadequacy of effector T-cell response in containment of tubercle bacilli is believed to result in the development of disseminated forms of tuberculosis (TB), such as miliary tuberculosis (MTB). Regulatory T cells (Treg) plausibly play a critical role in the immunopathogenesis of disseminated TB by suppression of effector immune response against Mycobacterium tuberculosis at the pathologic site(s). To understand the role of Treg cells in disseminated tuberculosis, we studied the frequency and function of Treg cells derived from the local disease site specimens (LDSS) of patients with TB pleural effusion and MTB as clinical models of contained and disseminated forms of disease, respectively.
  
  
  OBJECTIVE
  To (1) enumerate the frequency of Treg cells in bronchoalveolar lavage (BAL) fluid of patients with MTB and compare with that of peripheral blood, (2) study the role of Treg cells in suppression of local T-cell response, and (3) study the selective recruitment of Treg cells at the local disease site(s).
  
  
  METHODS
  Flow cytometry, reverse transcriptase polymerase chain reaction, and 3-(4,5-dimethylthythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-based cell proliferation assay.
  
  
  RESULTS
  Frequency of Treg cells (CD4(+)CD25(+)FoxP3(+)) was significantly higher in LDSS in MTB along with higher levels of FoxP3 mRNA. Importantly, FoxP3(+) Treg cells obtained from the BAL of patients with MTB predominantly produced IL-10 and could suppress the autologous T-cell proliferation in response to M. tuberculosis antigen.
  
  
  CONCLUSIONS
  Our results highlight the importance of Treg cells in suppression of effector immune response and their influence on bacillary dissemination, disease manifestation, and severity.
authors.affiliation: Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Prabhat K
authors.initials: PK
authors.lastname: Sharma
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Saha
authors.forename: Amar
authors.initials: A
authors.lastname: Singh
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
authors.forename: Dipendra K
authors.initials: DK
authors.lastname: Mitra
mesh_terms: D000293:Adolescent; D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D014391:Tuberculosis, Miliary / Q000276:immunology* / Q000503:physiopathology; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D016753:Interleukin-10