Document Detail

Longitudinal changes in CD4(+) T-cell memory responses induced by BCG vaccination of newborns.
MedLine Citation:
PMID:  23293360     Owner:  NLM     Status:  MEDLINE    
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.
Andreia P Soares; Cheong K C Kwong Chung; Terry Choice; E Jane Hughes; Gail Jacobs; Esme Janse van Rensburg; Gloria Khomba; Marwou de Kock; Lesedi Lerumo; Lebohang Makhethe; Mbulelo H Maneli; Bernadette Pienaar; Erica Smit; Nontobeko G Tena-Coki; Leandre van Wyk; W Henry Boom; Gilla Kaplan; Thomas J Scriba; Willem A Hanekom
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-04
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  207     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-28     Completed Date:  2013-04-18     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1084-94     Citation Subset:  AIM; IM    
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MeSH Terms
BCG Vaccine / administration & dosage,  immunology*
Biological Markers / blood
CD4-Positive T-Lymphocytes / immunology*
Cross-Sectional Studies
Flow Cytometry
Immunologic Memory*
Infant, Newborn / immunology*
Interferon-gamma / blood
Interleukin-2 / blood
Longitudinal Studies
Lymphocyte Activation
Mycobacterium tuberculosis / immunology
Time Factors
Treatment Outcome
Tuberculosis / immunology,  microbiology,  therapy
Tumor Necrosis Factor-alpha / blood
Vaccination / methods*
Grant Support
N01-AI-70022/AI/NIAID NIH HHS; R01-AI087915/AI/NIAID NIH HHS; //Wellcome Trust
Reg. No./Substance:
0/BCG Vaccine; 0/Biological Markers; 0/IL2 protein, human; 0/Interleukin-2; 0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma

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