title: CD4 T-cell cytokine correlates of diagnostic tests for latent tuberculous infection in HIV-1-infected subjects.
abstract: METHODS
  Public human immunodeficiency virus (HIV) clinic and tuberculosis (TB) clinics in Kampala, Uganda.
  
  
  OBJECTIVE
  To examine TB-specific CD4 T-cell single and polyfunctional cytokine correlates of clinical diagnostic tests for latent tuberculous infection (LTBI) in HIV-1-infected subjects.
  
  
  METHODS
  Thirty antiretroviral therapy-naïve HIV-1-infected adults without active TB disease underwent clinical tuberculin skin test (TST), interferon-gamma release assay (IGRA), and in vitro flow cytometry analysis on cells stimulated with purified protein derivative (PPD) and TB antigens early secreted antigenic target 6 + culture filtrate protein 10 (EC) for frequencies of interleukin (IL) 2, IL-17, interferon-gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) expressing cells.
  
  
  RESULTS
  PPD-specific CD4 T-cell expression of TNF-α and IFN-γ was higher in the TST-positive than in the TST-negative group. EC-specific CD4 T-cell expression of TNF-α and IL-2 was higher in the TST+ group than in the TST- group. Expression of both PPD and EC-specific expression of IL-2, IFN-γ and TNF-α were greater in IGRA-positive than in IGRA-negative subjects. The TST+ group exhibited greater polyfunctionality than the TST- group. All cytokine combinations that contained TNF-α correlated strongly with TST size.
  
  
  CONCLUSIONS
  While IL-2, IFN-γ and TNF-α correlate with clinical tests of LTBI, TNF-α is the dominant cytokine correlating with both TST size and magnitude of IGRA response.
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Geriatric Research Center Clinical Center, Louis Stokes Cleveland Veterans Administration, Cleveland, Ohio, USA.
authors.forename: P
authors.initials: P
authors.lastname: Van Epps
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sridaran
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: H
authors.initials: H
authors.lastname: Aung
authors.affiliation: Geriatric Research Center Clinical Center, Louis Stokes Cleveland Veterans Administration, Cleveland, Ohio, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Wilson
authors.affiliation: Geriatric Research Center Clinical Center, Louis Stokes Cleveland Veterans Administration, Cleveland, Ohio, USA; Case Western Reserve University Frances Payne Bolton School of Nursing, Cleveland, Ohio, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Burant
authors.affiliation: Department of Medicine, Makerere University, Kampala, Uganda.
authors.forename: M
authors.initials: M
authors.lastname: Nserko
authors.affiliation: Department of Medicine, Makerere University, Kampala, Uganda.
authors.forename: H
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Betts
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Toossi
authors.affiliation: Division of Infectious Diseases and HIV Medicine, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Geriatric Research Center Clinical Center, Louis Stokes Cleveland Veterans Administration, Cleveland, Ohio, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Canaday
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test / Q000379:methods; D014454:Uganda
chemical_list: D016207:Cytokines; D014373:Tuberculin