title: CD8+ T cells provide an immunologic signature of tuberculosis in young children.
abstract: BACKGROUND
  The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis.
  
  
  OBJECTIVE
  To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis.
  
  
  METHODS
  Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62).
  
  
  RESULTS
  The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups.
  
  
  CONCLUSIONS
  Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA. lancioni@ohsu.edu
authors.forename: Christina
authors.initials: C
authors.lastname: Lancioni
authors.forename: Melissa
authors.initials: M
authors.lastname: Nyendak
authors.forename: Sarah
authors.initials: S
authors.lastname: Kiguli
authors.forename: Sarah
authors.initials: S
authors.lastname: Zalwango
authors.forename: Tomi
authors.initials: T
authors.lastname: Mori
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.forename: Stephen
authors.initials: S
authors.lastname: Balyejusa
authors.forename: Megan
authors.initials: M
authors.lastname: Null
authors.forename: Joy
authors.initials: J
authors.lastname: Baseke
authors.forename: Deo
authors.initials: D
authors.lastname: Mulindwa
authors.forename: Laura
authors.initials: L
authors.lastname: Byrd
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Swarbrick
authors.forename: Christine
authors.initials: C
authors.lastname: Scott
authors.forename: Denise F
authors.initials: DF
authors.lastname: Johnson
authors.forename: LaShaunda
authors.initials: L
authors.lastname: Malone
authors.forename: Philipa
authors.initials: P
authors.lastname: Mudido-Musoke
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: David M
authors.initials: DM
authors.lastname: Lewinsohn
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Lewinsohn
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006760:Hospitalization; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018709:Statistics, Nonparametric; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014454:Uganda
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C505464:ESAT-6-CFP10 fusion protein; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma
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