tetano
Editor, Senior Moderator
J Infect Dis. 2014 Feb 20. [Epub ahead of print]
Plasmacytoid DC engagement by Flu vaccine as a surrogate strategy for driving Th1 responses in human neonatal settings.
Zhang X1, Casartelli N, Lemoine S, Mozeleski B, Azria E, Le Ray C, Schwartz O, Launay O, Leclerc C, Lo-Man R.
Author information
Abstract
Background. The elicitation of Th1 cellular immunity to eradicate intracellular pathogens is a challenging task due to the IL-12 deficit observed in early infancy.Methods. Screening cord blood responses to various pediatric vaccines and TLR agonists for innate responses and CD4 T cell differentiation.Results. We identified that non-adjuvanted inactivated trivalent influenza vaccine (TIV) was able to cosignal T cells for the production of IFN-g in a neonatal setting. This process includes the mobilization of neonatal plasmacytoid dendritic cells (pDC) as antigen-presenting cells (APC) that efficiently engage Th1 cells in an IL-12-independent, but type I interferon-dependent manner. In addition, cord blood pDCs efficiently cross-presented antigen to CD8 T cells. Importantly, activation by TIV mainly requires TLR7; however, R848/TLR7 and CpGB/TLR9 activated pDCs which poorly produced IFN-α induce neonatal Th2 responses.Conclusions. TLR pathway engagement in pDCs is necessary but not sufficient for a successful neonatal Th1 outcome. We provide evidence of a mature and functional neonatal immune system at the level of APCs and T cells and propose to implement the IFN-a/IFN-g axis in pediatric vaccination as a surrogate for the defective IL-12/IFN-g axis.
PMID:
24558121
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24558121
Plasmacytoid DC engagement by Flu vaccine as a surrogate strategy for driving Th1 responses in human neonatal settings.
Zhang X1, Casartelli N, Lemoine S, Mozeleski B, Azria E, Le Ray C, Schwartz O, Launay O, Leclerc C, Lo-Man R.
Author information
Abstract
Background. The elicitation of Th1 cellular immunity to eradicate intracellular pathogens is a challenging task due to the IL-12 deficit observed in early infancy.Methods. Screening cord blood responses to various pediatric vaccines and TLR agonists for innate responses and CD4 T cell differentiation.Results. We identified that non-adjuvanted inactivated trivalent influenza vaccine (TIV) was able to cosignal T cells for the production of IFN-g in a neonatal setting. This process includes the mobilization of neonatal plasmacytoid dendritic cells (pDC) as antigen-presenting cells (APC) that efficiently engage Th1 cells in an IL-12-independent, but type I interferon-dependent manner. In addition, cord blood pDCs efficiently cross-presented antigen to CD8 T cells. Importantly, activation by TIV mainly requires TLR7; however, R848/TLR7 and CpGB/TLR9 activated pDCs which poorly produced IFN-α induce neonatal Th2 responses.Conclusions. TLR pathway engagement in pDCs is necessary but not sufficient for a successful neonatal Th1 outcome. We provide evidence of a mature and functional neonatal immune system at the level of APCs and T cells and propose to implement the IFN-a/IFN-g axis in pediatric vaccination as a surrogate for the defective IL-12/IFN-g axis.
PMID:
24558121
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24558121