dc.contributor.author
Nowak, Anna
dc.contributor.author
Lock, Dominik
dc.contributor.author
Bacher, Petra
dc.contributor.author
Hohnstein, Thordis
dc.contributor.author
Vogt, Katrin
dc.contributor.author
Gottfreund, Judith
dc.contributor.author
Giehr, Pascal
dc.contributor.author
Polansky, Julia K.
dc.contributor.author
Sawitzki, Birgit
dc.contributor.author
Kaiser, Andrew
dc.contributor.author
Walter, Joern
dc.contributor.author
Scheffold, Alexander
dc.date.accessioned
2018-06-08T10:53:41Z
dc.date.available
2018-03-05T08:46:36.740Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21289
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24584
dc.description.abstract
Regulatory T cells (Tregs) are an attractive therapeutic tool for several
different immune pathologies. Therapeutic Treg application often requires
prolonged in vitro culture to generate sufficient Treg numbers or to optimize
their functionality, e.g., via genetic engineering of their antigen receptors.
However, purity of clinical Treg expansion cultures is highly variable, and
currently, it is impossible to identify and separate stable Tregs from
contaminating effector T cells, either ex vivo or after prior expansion. This
represents a major obstacle for quality assurance of expanded Tregs and raises
significant safety concerns. Here, we describe a Treg activation signature
that allows identification and sorting of epigenetically imprinted Tregs even
after prolonged in vitro culture. We show that short-term reactivation
resulted in expression of CD137 but not CD154 on stable FoxP3+ Tregs that
displayed a demethylated Treg-specific demethylated region, high suppressive
potential, and lack of inflammatory cytokine expression. We also applied this
Treg activation signature for rapid testing of chimeric antigen receptor
functionality in human Tregs and identified major differences in the signaling
requirements regarding CD137 versus CD28 costimulation. Taken together,
CD137+CD154− expression emerges as a universal Treg activation signature ex
vivo and upon in vitro expansion allowing the identification and isolation of
epigenetically stable antigen-activated Tregs and providing a means for their
rapid functional testing in vitro.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
regulatory T cells
dc.subject
chimeric antigen receptor
dc.subject
adoptive regulatory T cell therapy
dc.subject
regulatory T cell stability
dc.subject
regulatory T cell expansion
dc.subject
regulatory T cell signaling
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
CD137+CD154− Expression As a Regulatory T Cell (Treg)-Specific Activation
Signature for Identification and Sorting of Stable Human Tregs from In Vitro
Expansion Cultures
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Front. Immunol. - 9 (2018), Artikel Nr. 199
dcterms.bibliographicCitation.doi
10.3389/fimmu.2018.00199
dcterms.bibliographicCitation.url
http://doi.org/10.3389/fimmu.2018.00199
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000029195
refubium.note.author
Der Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009501
dcterms.accessRights.openaire
open access