The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.

BACKGROUND:The Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycoba...

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Main Authors: Christel Zufferey, Susie Germano, Binita Dutta, Nicole Ritz, Nigel Curtis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3789697?pdf=render
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author Christel Zufferey
Susie Germano
Binita Dutta
Nicole Ritz
Nigel Curtis
author_facet Christel Zufferey
Susie Germano
Binita Dutta
Nicole Ritz
Nigel Curtis
author_sort Christel Zufferey
collection DOAJ
description BACKGROUND:The Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycobacterial-specific immune response is of increasing interest. METHODS:Participants in four age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was analyzed for NK and T cell markers, and intracellular IFNgamma (IFNγ) by flow cytometry. Total functional IFNγ response was calculated using integrated median fluorescence intensity (iMFI). RESULTS:In infants and children, CD4 and CD4-CD8- (double-negative (DN)) T cells were the main IFNγ-expressing cells representing 43-56% and 27-37% of total CD3+ IFNγ+ T cells respectively. The iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the greatest differences seen in infants immunized at birth (p=0.002) or 2 months of age (p<0.0001). When NK cells were included in the analysis, they accounted for the majority of total IFNγ-expressing cells and, together with DN Vδ2 γδ T cells, had the highest iMFI in infants immunized at birth or 2 months of age. CONCLUSION:In addition to CD4 T cells, NK cells and DN T cells, including Vδ2 γδ T cells, are the key populations producing IFNγ in response to BCG immunization in infants and children. This suggests that innate immunity and unconventional T cells play a greater role in the mycobacterial immune response than previously recognized and should be considered in the design and assessment of novel tuberculosis vaccines.
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spelling doaj.art-49aab3b6326b4b65a15df67879f43f832022-12-21T23:51:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7733410.1371/journal.pone.0077334The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.Christel ZuffereySusie GermanoBinita DuttaNicole RitzNigel CurtisBACKGROUND:The Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine is given to >120 million infants each year worldwide. Most studies investigating the immune response to BCG have focused on adaptive immunity. However the importance of TCR-gamma/delta (γδ) T cells and NK cells in the mycobacterial-specific immune response is of increasing interest. METHODS:Participants in four age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was analyzed for NK and T cell markers, and intracellular IFNgamma (IFNγ) by flow cytometry. Total functional IFNγ response was calculated using integrated median fluorescence intensity (iMFI). RESULTS:In infants and children, CD4 and CD4-CD8- (double-negative (DN)) T cells were the main IFNγ-expressing cells representing 43-56% and 27-37% of total CD3+ IFNγ+ T cells respectively. The iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the greatest differences seen in infants immunized at birth (p=0.002) or 2 months of age (p<0.0001). When NK cells were included in the analysis, they accounted for the majority of total IFNγ-expressing cells and, together with DN Vδ2 γδ T cells, had the highest iMFI in infants immunized at birth or 2 months of age. CONCLUSION:In addition to CD4 T cells, NK cells and DN T cells, including Vδ2 γδ T cells, are the key populations producing IFNγ in response to BCG immunization in infants and children. This suggests that innate immunity and unconventional T cells play a greater role in the mycobacterial immune response than previously recognized and should be considered in the design and assessment of novel tuberculosis vaccines.http://europepmc.org/articles/PMC3789697?pdf=render
spellingShingle Christel Zufferey
Susie Germano
Binita Dutta
Nicole Ritz
Nigel Curtis
The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
PLoS ONE
title The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
title_full The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
title_fullStr The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
title_full_unstemmed The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
title_short The contribution of non-conventional T cells and NK cells in the mycobacterial-specific IFNγ response in Bacille Calmette-Guérin (BCG)-immunized infants.
title_sort contribution of non conventional t cells and nk cells in the mycobacterial specific ifnγ response in bacille calmette guerin bcg immunized infants
url http://europepmc.org/articles/PMC3789697?pdf=render
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