Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

Hdl Handle:
http://hdl.handle.net/10147/207408
Title:
Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.
Authors:
McCarron, Mark; Reen, Denis J
Affiliation:
Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin,, Ireland. mark.mccarron@ucd.ie
Citation:
J Immunol. 2009 Jan 1;182(1):55-62.
Journal:
Journal of immunology (Baltimore, Md. : 1950)
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207408
PubMed ID:
19109135
Abstract:
In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate's natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.
Language:
eng
MeSH:
Adjuvants, Immunologic/chemical synthesis/*pharmacology; Antigen-Presenting Cells/drug effects/immunology/metabolism; CD8-Positive T-Lymphocytes/drug effects/*immunology/*metabolism; Cell Proliferation/drug effects; Cells, Cultured; Dipeptides/pharmacology; Fetal Blood/cytology/drug effects/immunology/metabolism; Flagellin/pharmacology; Humans; Immunity, Cellular/drug effects; Infant, Newborn; Ligands; Lipoproteins/pharmacology; Lymphocyte Activation/drug effects/*immunology; Toll-Like Receptor 2/agonists/biosynthesis/genetics/*metabolism; Toll-Like Receptor 5/agonists/biosynthesis/genetics/*metabolism
ISSN:
1550-6606 (Electronic); 0022-1767 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMcCarron, Marken_GB
dc.contributor.authorReen, Denis Jen_GB
dc.date.accessioned2012-02-01T10:24:15Z-
dc.date.available2012-02-01T10:24:15Z-
dc.date.issued2012-02-01T10:24:15Z-
dc.identifier.citationJ Immunol. 2009 Jan 1;182(1):55-62.en_GB
dc.identifier.issn1550-6606 (Electronic)en_GB
dc.identifier.issn0022-1767 (Linking)en_GB
dc.identifier.pmid19109135en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207408-
dc.description.abstractIn conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate's natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.en_GB
dc.language.isoengen_GB
dc.subject.meshAdjuvants, Immunologic/chemical synthesis/*pharmacologyen_GB
dc.subject.meshAntigen-Presenting Cells/drug effects/immunology/metabolismen_GB
dc.subject.meshCD8-Positive T-Lymphocytes/drug effects/*immunology/*metabolismen_GB
dc.subject.meshCell Proliferation/drug effectsen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshDipeptides/pharmacologyen_GB
dc.subject.meshFetal Blood/cytology/drug effects/immunology/metabolismen_GB
dc.subject.meshFlagellin/pharmacologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunity, Cellular/drug effectsen_GB
dc.subject.meshInfant, Newbornen_GB
dc.subject.meshLigandsen_GB
dc.subject.meshLipoproteins/pharmacologyen_GB
dc.subject.meshLymphocyte Activation/drug effects/*immunologyen_GB
dc.subject.meshToll-Like Receptor 2/agonists/biosynthesis/genetics/*metabolismen_GB
dc.subject.meshToll-Like Receptor 5/agonists/biosynthesis/genetics/*metabolismen_GB
dc.titleActivated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.en_GB
dc.contributor.departmentChildren's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin,, Ireland. mark.mccarron@ucd.ieen_GB
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en_GB
dc.description.provinceLeinster-

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