title: Regulatory T cells modulate Th17 responses in patients with positive tuberculin skin test results.
abstract: BACKGROUND
  The factors governing latency in tuberculosis are not well understood but appear to involve both the pathogen and the host. We have used tuberculin skin test (TST) positivity as a tool to study cytokine responses in latent tuberculosis.
  
  
  METHODS
  To identify the host factors that are important in the maintenance of TST positivity, we examined mycobacteria-specific immune responses of TST-positive (latent tuberculosis) or TST-negative individuals in South India, where TST positivity can define tuberculosis latency.
  
  
  RESULTS
  Although purified protein derivative-specific and Mycobacterium tuberculosis culture filtrate antigen-specific Th1 and Th2 cytokines were not statistically significantly different between the 2 groups, the Th17 cytokines (interleukin 17 and interleukin 23) were statistically significantly decreased in TST-positive individuals, compared with those in TST-negative individuals. This Th17 cytokine modulation was associated with statistically significantly increased expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and Foxp3. Although CTLA-4 blockade failed to restore full production of interleukin 17 and interleukin 23 in TST-positive individuals, depletion of regulatory T cells significantly increased production of these cytokines.
  
  
  CONCLUSIONS
  TST positivity is characterized by increased activity of regulatory T cells and a coincident down-regulation of the Th17 response.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, India. sbabu@mail.nih.gov
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
authors.forename: Sajid Q
authors.initials: SQ
authors.lastname: Bhat
authors.forename: N Pavan
authors.initials: NP
authors.lastname: Kumar
authors.forename: V
authors.initials: V
authors.lastname: Kumaraswami
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism*; D055985:Latent Tuberculosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053759:Interleukin-23