title: Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Guérin vaccination of newborns.
abstract: BACKGROUND
  Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells.
  
  
  OBJECTIVE
  We tested whether this outcome correlates with protection against childhood TB disease after newborn vaccination with bacillus Calmette-Guérin (BCG).
  
  
  METHODS
  Whole blood from 10-week-old infants, routinely vaccinated with BCG at birth, was incubated with BCG for 12 hours, followed by cryopreservation for intracellular cytokine analysis. Infants were followed for 2 years to identify those who developed culture-positive TB-these infants were regarded as not protected against TB. Infants who did not develop TB disease despite exposure to TB in the household, and another group of randomly selected infants who were never evaluated for TB, were also identified-these groups were regarded as protected against TB. Cells from these groups were thawed, and CD4, CD8, and γδ T cell-specific expression of IFN-γ, TNF-α, IL-2, and IL-17 measured by flow cytometry.
  
  
  RESULTS
  A total of 5,662 infants were enrolled; 29 unprotected and two groups of 55 protected infants were identified. There was no difference in frequencies of BCG-specific CD4, CD8, and γδ T cells between the three groups of infants. Although BCG induced complex patterns of intracellular cytokine expression, there were no differences between protected and unprotected infants.
  
  
  CONCLUSIONS
  The frequency and cytokine profile of mycobacteria-specific T cells did not correlate with protection against TB. Critical components of immunity against Mycobacterium tuberculosis, such as CD4 T cell IFN-γ production, may not necessarily translate into immune correlates of protection against TB disease.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Benjamin M N
authors.initials: BM
authors.lastname: Kagina
authors.forename: Brian
authors.initials: B
authors.lastname: Abel
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Alana
authors.initials: A
authors.lastname: Keyser
authors.forename: Andreia
authors.initials: A
authors.lastname: Soares
authors.forename: Hoyam
authors.initials: H
authors.lastname: Gamieldien
authors.forename: Mzwandile
authors.initials: M
authors.lastname: Sidibana
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gelderbloem
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.forename: Gregory
authors.initials: G
authors.lastname: Hussey
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D001500:BCG Vaccine / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood; D011446:Prospective Studies; D013019:South Africa; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D007371:Interferon-gamma