Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/600466
Title:
Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.
Authors:
Franckaert, Dean; Dooley, James; Roos, Evelyne; Floess, Stefan; Huehn, Jochen; Luche, Herve; Fehling, Hans Joerg; Liston, Adrian; Linterman, Michelle A; Schlenner, Susan M
Abstract:
Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including R26-RFP). This hypomorphism and 'leaky' expression of the Foxp3-CreYFP allele should be considered when analysing the conditionally mutated Treg.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells. 2015, 93 (4):417-23 Immunol. Cell Biol.
Journal:
Immunology and cell biology
Issue Date:
Apr-2015
URI:
http://hdl.handle.net/10033/600466
DOI:
10.1038/icb.2014.108
PubMed ID:
25533288
Type:
Article
Language:
en
ISSN:
1440-1711
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorFranckaert, Deanen
dc.contributor.authorDooley, Jamesen
dc.contributor.authorRoos, Evelyneen
dc.contributor.authorFloess, Stefanen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorLuche, Herveen
dc.contributor.authorFehling, Hans Joergen
dc.contributor.authorListon, Adrianen
dc.contributor.authorLinterman, Michelle Aen
dc.contributor.authorSchlenner, Susan Men
dc.date.accessioned2016-03-02T11:43:24Zen
dc.date.available2016-03-02T11:43:24Zen
dc.date.issued2015-04en
dc.identifier.citationPromiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells. 2015, 93 (4):417-23 Immunol. Cell Biol.en
dc.identifier.issn1440-1711en
dc.identifier.pmid25533288en
dc.identifier.doi10.1038/icb.2014.108en
dc.identifier.urihttp://hdl.handle.net/10033/600466en
dc.description.abstractCostimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including R26-RFP). This hypomorphism and 'leaky' expression of the Foxp3-CreYFP allele should be considered when analysing the conditionally mutated Treg.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntigens, CD28en
dc.subject.meshAutoimmunityen
dc.subject.meshCell Differentiationen
dc.subject.meshCell Lineageen
dc.subject.meshCell Survivalen
dc.subject.meshClonal Selection, Antigen-Mediateden
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshGene Expression Regulation, Developmentalen
dc.subject.meshHomeostasisen
dc.subject.meshMiceen
dc.subject.meshMice, Transgenicen
dc.subject.meshSignal Transductionen
dc.subject.meshT-Lymphocyte Subsetsen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titlePromiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3⁺ and Foxp3⁻ T cells.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalImmunology and cell biologyen

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