title: Longitudinal changes in CD4(+) T-cell memory responses induced by BCG vaccination of newborns.
abstract: BACKGROUND
  Improved vaccination strategies against tuberculosis are needed, such as approaches to boost immunity induced by the current vaccine, BCG. Design of these strategies has been hampered by a lack of knowledge of the kinetics of the human host response induced by neonatal BCG vaccination. Furthermore, the functional and phenotypic attributes of BCG-induced long-lived memory T-cell responses remain unclear.
  
  
  METHODS
  We assessed the longitudinal CD4 T-cell response following BCG vaccination of human newborns. The kinetics, function, and phenotype of these cells were measured using flow cytometric whole-blood assays.
  
  
  RESULTS
  We showed that the BCG-specific CD4 T-cell response peaked 6-10 weeks after vaccination and gradually waned over the first year of life. Highly activated T-helper 1 cells, predominantly expressing interferon γ, tumor necrosis factor α, and/or interleukin 2, were present at the peak response. Following contraction, BCG-specific CD4 T cells expressed high levels of Bcl-2 and displayed a predominant CD45RACCR7 central memory phenotype. However, cytokine and cytotoxic marker expression by these cells was more characteristic of effector memory cells.
  
  
  CONCLUSIONS
  Our findings suggest that boosting of BCG-primed CD4 T cells with heterologous tuberculosis vaccines may be best after 14 weeks of age, once an established memory response has developed.
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: Andreia P
authors.initials: AP
authors.lastname: Soares
authors.forename: Cheong K C
authors.initials: CK
authors.lastname: Kwong Chung
authors.forename: Terry
authors.initials: T
authors.lastname: Choice
authors.forename: E Jane
authors.initials: EJ
authors.lastname: Hughes
authors.forename: Gail
authors.initials: G
authors.lastname: Jacobs
authors.forename: Esme Janse
authors.initials: EJ
authors.lastname: van Rensburg
authors.forename: Gloria
authors.initials: G
authors.lastname: Khomba
authors.forename: Marwou
authors.initials: M
authors.lastname: de Kock
authors.forename: Lesedi
authors.initials: L
authors.lastname: Lerumo
authors.forename: Lebohang
authors.initials: L
authors.lastname: Makhethe
authors.forename: Mbulelo H
authors.initials: MH
authors.lastname: Maneli
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pienaar
authors.forename: Erica
authors.initials: E
authors.lastname: Smit
authors.forename: Nontobeko G
authors.initials: NG
authors.lastname: Tena-Coki
authors.forename: Leandre
authors.initials: L
authors.lastname: van Wyk
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
mesh_terms: D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007231:Infant, Newborn / Q000276:immunology*; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014611:Vaccination / Q000379:methods*
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; C508594:IL2 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma