2.50
Hdl Handle:
http://hdl.handle.net/10033/304568
Title:
Foxp3+ regulatory T cells are required for recovery from severe sepsis.
Authors:
Kühlhorn, Franziska; Rath, Matthias; Schmoeckel, Katrin; Cziupka, Katharina; Nguyen, Huu Hung; Hildebrandt, Petra; Hünig, Thomas; Sparwasser, Tim; Huehn, Jochen; Pötschke, Christian; Bröker, Barbara M
Abstract:
The role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of CD4(+)Foxp3(+) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.
Affiliation:
Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
Citation:
Foxp3+ regulatory T cells are required for recovery from severe sepsis. 2013, 8 (5):e65109 PLoS ONE
Journal:
PloS one
Issue Date:
2013
URI:
http://hdl.handle.net/10033/304568
DOI:
10.1371/journal.pone.0065109
PubMed ID:
23724126
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS)

Full metadata record

DC FieldValue Language
dc.contributor.authorKühlhorn, Franziskaen
dc.contributor.authorRath, Matthiasen
dc.contributor.authorSchmoeckel, Katrinen
dc.contributor.authorCziupka, Katharinaen
dc.contributor.authorNguyen, Huu Hungen
dc.contributor.authorHildebrandt, Petraen
dc.contributor.authorHünig, Thomasen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorPötschke, Christianen
dc.contributor.authorBröker, Barbara Men
dc.date.accessioned2013-10-24T10:19:39Z-
dc.date.available2013-10-24T10:19:39Z-
dc.date.issued2013-
dc.identifier.citationFoxp3+ regulatory T cells are required for recovery from severe sepsis. 2013, 8 (5):e65109 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid23724126-
dc.identifier.doi10.1371/journal.pone.0065109-
dc.identifier.urihttp://hdl.handle.net/10033/304568-
dc.description.abstractThe role of regulatory T cells (Tregs) in bacterial sepsis remains controversial because antibody-mediated depletion experiments gave conflicting results. We employed DEREG mice (DEpletion of REGulatory T cells) and a caecal ligation and puncture model to elucidate the role of CD4(+)Foxp3(+) Tregs in sepsis. In DEREG mice natural Tregs can be visualized easily and selectively depleted by diphtheria toxin because the animals express the diphtheria toxin receptor and enhanced green fluorescent protein as a fusion protein under the control of the foxp3 locus. We confirmed rapid Treg-activation and an increased ratio of Tregs to Teffs in sepsis. Nevertheless, 24 h after sepsis induction, Treg-depleted and control mice showed equally strong inflammation, immune cell immigration into the peritoneum and bacterial dissemination. During the first 36 h of disease survival was not influenced by Treg-depletion. Later, however, only Treg-competent animals recovered from the insult. We conclude that the suppressive capacity of Tregs is not sufficient to control overwhelming inflammation and early mortality, but is a prerequisite for the recovery from severe sepsis.en
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen
dc.titleFoxp3+ regulatory T cells are required for recovery from severe sepsis.en
dc.typeArticleen
dc.contributor.departmentInstitute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.en
dc.identifier.journalPloS oneen

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