Neonatal CD8+ T-cell differentiation is dependent on interleukin-12.

Hdl Handle:
http://hdl.handle.net/10147/207463
Title:
Neonatal CD8+ T-cell differentiation is dependent on interleukin-12.
Authors:
McCarron, Mark J; Reen, Denis J
Affiliation:
National Children's Research Centre, Our Lady's Children's Hospital, Crumlin,, Dublin, Ireland. mark.mccarron@ucd.ie
Citation:
Hum Immunol. 2010 Dec;71(12):1172-9. Epub 2010 Sep 16.
Journal:
Human immunology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207463
DOI:
10.1016/j.humimm.2010.09.004
PubMed ID:
20849902
Abstract:
Neonatal CD8(+) T-cell activation is significantly impaired compared with that in adults. Recent studies have demonstrated that interleukin (IL)-12 is necessary as a third signal, in addition to antigen and co-stimulation, to authorize the differentiation of naive CD8(+) T cells. We examined whether human neonatal CD8(+) T cells, which possess an exclusively naive T-cell phenotype, required a third signal to authorize a productive T-cell response. IL-12 enhanced activated naive CD8(+) T-cell survival, expansion, CD25 expression, and IL-2 production. Activated CD8(+) T cells produced interferon-gamma and intracellular granzyme B and were cytotoxic only in the presence of IL-12. Sustained IL-12 signaling for 72 hours was required for optimal interferon-gamma production. IL-12, in concert with T cell receptor (TCR) stimulation, sustained late-stage (48-72 hours) intracellular phosphorylation and particularly total protein levels of the proximal TCR components, Lck, and CD3xi. The requirement for a third signal for productive human neonatal CD8(+) T-cell differentiation may have implications for neonatal vaccination strategies.
Language:
eng
MeSH:
CD8-Positive T-Lymphocytes/*cytology/immunology/metabolism; *Cell Differentiation; Fetal Blood/cytology; Humans; Infant, Newborn; Interferon-gamma/biosynthesis; Interleukin-12/immunology/*metabolism; Lymphocyte Activation; Receptors, Antigen, T-Cell/immunology/metabolism; Signal Transduction
ISSN:
1879-1166 (Electronic); 0198-8859 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMcCarron, Mark Jen_GB
dc.contributor.authorReen, Denis Jen_GB
dc.date.accessioned2012-02-01T10:25:38Z-
dc.date.available2012-02-01T10:25:38Z-
dc.date.issued2012-02-01T10:25:38Z-
dc.identifier.citationHum Immunol. 2010 Dec;71(12):1172-9. Epub 2010 Sep 16.en_GB
dc.identifier.issn1879-1166 (Electronic)en_GB
dc.identifier.issn0198-8859 (Linking)en_GB
dc.identifier.pmid20849902en_GB
dc.identifier.doi10.1016/j.humimm.2010.09.004en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207463-
dc.description.abstractNeonatal CD8(+) T-cell activation is significantly impaired compared with that in adults. Recent studies have demonstrated that interleukin (IL)-12 is necessary as a third signal, in addition to antigen and co-stimulation, to authorize the differentiation of naive CD8(+) T cells. We examined whether human neonatal CD8(+) T cells, which possess an exclusively naive T-cell phenotype, required a third signal to authorize a productive T-cell response. IL-12 enhanced activated naive CD8(+) T-cell survival, expansion, CD25 expression, and IL-2 production. Activated CD8(+) T cells produced interferon-gamma and intracellular granzyme B and were cytotoxic only in the presence of IL-12. Sustained IL-12 signaling for 72 hours was required for optimal interferon-gamma production. IL-12, in concert with T cell receptor (TCR) stimulation, sustained late-stage (48-72 hours) intracellular phosphorylation and particularly total protein levels of the proximal TCR components, Lck, and CD3xi. The requirement for a third signal for productive human neonatal CD8(+) T-cell differentiation may have implications for neonatal vaccination strategies.en_GB
dc.language.isoengen_GB
dc.subject.meshCD8-Positive T-Lymphocytes/*cytology/immunology/metabolismen_GB
dc.subject.mesh*Cell Differentiationen_GB
dc.subject.meshFetal Blood/cytologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInfant, Newbornen_GB
dc.subject.meshInterferon-gamma/biosynthesisen_GB
dc.subject.meshInterleukin-12/immunology/*metabolismen_GB
dc.subject.meshLymphocyte Activationen_GB
dc.subject.meshReceptors, Antigen, T-Cell/immunology/metabolismen_GB
dc.subject.meshSignal Transductionen_GB
dc.titleNeonatal CD8+ T-cell differentiation is dependent on interleukin-12.en_GB
dc.contributor.departmentNational Children's Research Centre, Our Lady's Children's Hospital, Crumlin,, Dublin, Ireland. mark.mccarron@ucd.ieen_GB
dc.identifier.journalHuman immunologyen_GB
dc.description.provinceLeinster-

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