The adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/203749
Title:
The adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells.
Authors:
Olivier, Aurélie; Sainz-Perez, Alexander; Dong, Hui; Sparwasser, Tim; Majlessi, Laleh; Leclerc, Claude
Abstract:
TLR agonists have been suggested to directly impact Tregs, thereby enhancing or reversing their suppressive function. Here, in order to select TLR agonists leading to potent effector T-cell responses, while minimizing Treg inhibitory function, we used a model antigen, covalently linked to an inert delivery system, combined with a large panel of TLR agonists, for the immunization of mice with an attenuated/depleted or intact Treg subset. We observed that the negative modulation of effector CD4(+) T cells exerted by Tregs cannot be circumvented, whatever the TLR agonist used as adjuvant. To better understand the impact of TLR agonists on Tregs, we investigated (i) the TLR expression profile of highly purified CD4(+) Foxp3(+) Tregs, at steady state or subsequent to in vivo activation by TLR agonists and (ii) the Treg phenotype after in vivo and in vitro activation by TLR agonists. Our results demonstrate that TLR agonists, as single signal inducers, are not able to directly activate Tregs. The phenotypic Treg activation observed in vivo, following TLR administration, does not result from cross-talk with conventional T cells but is rather a consequence of the interaction with other immune cell type(s).
Affiliation:
Department of Immunology, Paris, France.
Citation:
The adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells. 2011, 41 (8):2303-13 Eur. J. Immunol.
Journal:
European journal of immunology
Issue Date:
Aug-2011
URI:
http://hdl.handle.net/10033/203749
DOI:
10.1002/eji.201041387
PubMed ID:
21538349
Type:
Article
Language:
en
ISSN:
1521-4141
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorOlivier, Aurélieen
dc.contributor.authorSainz-Perez, Alexanderen
dc.contributor.authorDong, Huien
dc.contributor.authorSparwasser, Timen
dc.contributor.authorMajlessi, Lalehen
dc.contributor.authorLeclerc, Claudeen
dc.date.accessioned2012-01-19T15:03:59Z-
dc.date.available2012-01-19T15:03:59Z-
dc.date.issued2011-08-
dc.identifier.citationThe adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells. 2011, 41 (8):2303-13 Eur. J. Immunol.en
dc.identifier.issn1521-4141-
dc.identifier.pmid21538349-
dc.identifier.doi10.1002/eji.201041387-
dc.identifier.urihttp://hdl.handle.net/10033/203749-
dc.description.abstractTLR agonists have been suggested to directly impact Tregs, thereby enhancing or reversing their suppressive function. Here, in order to select TLR agonists leading to potent effector T-cell responses, while minimizing Treg inhibitory function, we used a model antigen, covalently linked to an inert delivery system, combined with a large panel of TLR agonists, for the immunization of mice with an attenuated/depleted or intact Treg subset. We observed that the negative modulation of effector CD4(+) T cells exerted by Tregs cannot be circumvented, whatever the TLR agonist used as adjuvant. To better understand the impact of TLR agonists on Tregs, we investigated (i) the TLR expression profile of highly purified CD4(+) Foxp3(+) Tregs, at steady state or subsequent to in vivo activation by TLR agonists and (ii) the Treg phenotype after in vivo and in vitro activation by TLR agonists. Our results demonstrate that TLR agonists, as single signal inducers, are not able to directly activate Tregs. The phenotypic Treg activation observed in vivo, following TLR administration, does not result from cross-talk with conventional T cells but is rather a consequence of the interaction with other immune cell type(s).en
dc.language.isoenen
dc.subject.meshAdjuvants, Immunologicen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshAnimalsen
dc.subject.meshCD4-Positive T-Lymphocytesen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshGene Expression Profilingen
dc.subject.meshGreen Fluorescent Proteinsen
dc.subject.meshImidazolesen
dc.subject.meshLipopolysaccharidesen
dc.subject.meshLymphocyte Activationen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshMice, Transgenicen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshOligodeoxyribonucleotidesen
dc.subject.meshOvalbuminen
dc.subject.meshPeptide Fragmentsen
dc.subject.meshPoly I-Cen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshToll-Like Receptorsen
dc.subject.meshZymosanen
dc.titleThe adjuvant effect of TLR agonists on CD4(+) effector T cells is under the indirect control of regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentDepartment of Immunology, Paris, France.en
dc.identifier.journalEuropean journal of immunologyen

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