Document Detail

Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Guérin vaccination of newborns.
MedLine Citation:
PMID:  20558627     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Immunogenicity of new tuberculosis (TB) vaccines is commonly assessed by measuring the frequency and cytokine expression profile of T cells.
OBJECTIVES: 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.
MEASUREMENTS AND MAIN 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.
Benjamin M N Kagina; Brian Abel; Thomas J Scriba; Elizabeth J Hughes; Alana Keyser; Andreia Soares; Hoyam Gamieldien; Mzwandile Sidibana; Mark Hatherill; Sebastian Gelderbloem; Hassan Mahomed; Anthony Hawkridge; Gregory Hussey; Gilla Kaplan; Willem A Hanekom;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-06-17
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  182     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-15     Completed Date:  2010-11-15     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1073-9     Citation Subset:  AIM; IM    
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.
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MeSH Terms
BCG Vaccine / immunology*
CD4 Lymphocyte Count
Case-Control Studies
Cytokines / blood,  immunology
Infant, Newborn
Interferon-gamma / blood
Prospective Studies
South Africa
Tuberculosis / immunology,  prevention & control*
Grant Support
Reg. No./Substance:
0/BCG Vaccine; 0/Cytokines; 82115-62-6/Interferon-gamma

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