title: Bacillus Calmette-Guérin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles.
abstract: The immune response to vaccination with bacillus Calmette-Guérin (BCG), the only tuberculosis vaccine available, has not been fully characterized. We used multiparameter flow cytometry to examine specific T cell cytokine production and phenotypic profiles in blood from 10-wk-old infants routinely vaccinated with BCG at birth. Ex vivo stimulation of whole blood with BCG for 12 h induced expression of predominantly IFN-gamma, IL-2, and TNF-alpha in CD4+ T cells in seven distinct cytokine combinations. IL-4 and IL-10 expression was detected in CD4+ T cells at low frequencies and only in cells that did not coexpress type 1 cytokines. Specific CD8+ T cells were less frequent than CD4+ T cells and produced mainly IFN-gamma and/or IL-2 and less TNF-alpha, IL-4, and IL-10. Importantly, many mycobacteria-specific CD4+ and CD8+ T cells did not produce IFN-gamma. The predominant phenotype of BCG-specific type 1 T cells was that of effector cells, i.e., CD45RA-CCR7-CD27+, which may reflect persistence of Mycobacterium bovis BCG in infants until 10 wk of age. Among five phenotypic patterns of CD4+ T cells, central memory cells were more likely to be IL-2+ and effector cells were more likely to be IFN-gamma+. We concluded that neonatal vaccination with BCG induces T cells with a complex pattern of cytokine expression and phenotypes. Measuring IFN-gamma production alone underestimates the magnitude and complexity of the host cytokine response to BCG vaccination and may not be an optimal readout in studies of BCG and novel tuberculosis vaccination.
authors.affiliation: South African TB/Institute of Infectious Diseases and Molecular Medicine and School of Child and Adolescent Health, Vaccine Initiative, University of Cape Town, Cape Town, South Africa.
authors.forename: Andreia P
authors.initials: AP
authors.lastname: Soares
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Sarah
authors.initials: S
authors.lastname: Joseph
authors.forename: Ryhor
authors.initials: R
authors.lastname: Harbacheuski
authors.forename: Rose Ann
authors.initials: RA
authors.lastname: Murray
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Gelderbloem
authors.forename: Anthony
authors.initials: A
authors.lastname: Hawkridge
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Hussey
authors.forename: Holden
authors.initials: H
authors.lastname: Maecker
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000145:classification; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma