IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.

2.50
Hdl Handle:
http://hdl.handle.net/10033/305442
Title:
IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.
Authors:
Schmitz, Iwana; Schneider, Christoph; Fröhlich, Anja; Frebel, Helge; Christ, Daniel; Leonard, Warren J; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Oxenius, Annette; Freigang, Stefan; Kopf, Manfred
Abstract:
Foxp3+ regulatory T (Treg) cells are essential for the maintenance of immune homeostasis and tolerance. During viral infections, Treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral T cell responses and promote virus persistence. We report here that the fast-replicating LCMV strain Docile triggers a massive expansion of the Treg population that directly correlates with the size of the virus inoculum and its tendency to establish a chronic, persistent infection. This Treg cell proliferation was greatly enhanced in IL-21R-/- mice and depletion of Treg cells partially rescued defective CD8+ T cell cytokine responses and improved viral clearance in some but not all organs. Notably, IL-21 inhibited Treg cell expansion in a cell intrinsic manner. Moreover, experimental augmentation of Treg cells driven by injection of IL-2/anti-IL-2 immune complexes drastically impaired the functionality of the antiviral T cell response and impeded virus clearance. As a consequence, mice became highly susceptible to chronic infection following exposure to low virus doses. These findings reveal virus-driven Treg cell proliferation as potential evasion strategy that facilitates T cell exhaustion and virus persistence. Furthermore, they suggest that besides its primary function as a direct survival signal for antiviral CD8+ T cells during chronic infections, IL-21 may also indirectly promote CD8+ T cell poly-functionality by restricting the suppressive activity of infection-induced Treg cells.
Affiliation:
Molecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.
Citation:
IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. 2013, 9 (5):e1003362 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
May-2013
URI:
http://hdl.handle.net/10033/305442
DOI:
10.1371/journal.ppat.1003362
PubMed ID:
23696736
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorSchmitz, Iwanaen
dc.contributor.authorSchneider, Christophen
dc.contributor.authorFröhlich, Anjaen
dc.contributor.authorFrebel, Helgeen
dc.contributor.authorChrist, Danielen
dc.contributor.authorLeonard, Warren Jen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorOxenius, Annetteen
dc.contributor.authorFreigang, Stefanen
dc.contributor.authorKopf, Manfreden
dc.date.accessioned2013-11-15T14:37:38Zen
dc.date.available2013-11-15T14:37:38Zen
dc.date.issued2013-05en
dc.identifier.citationIL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. 2013, 9 (5):e1003362 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid23696736en
dc.identifier.doi10.1371/journal.ppat.1003362en
dc.identifier.urihttp://hdl.handle.net/10033/305442en
dc.description.abstractFoxp3+ regulatory T (Treg) cells are essential for the maintenance of immune homeostasis and tolerance. During viral infections, Treg cells can limit the immunopathology resulting from excessive inflammation, yet potentially inhibit effective antiviral T cell responses and promote virus persistence. We report here that the fast-replicating LCMV strain Docile triggers a massive expansion of the Treg population that directly correlates with the size of the virus inoculum and its tendency to establish a chronic, persistent infection. This Treg cell proliferation was greatly enhanced in IL-21R-/- mice and depletion of Treg cells partially rescued defective CD8+ T cell cytokine responses and improved viral clearance in some but not all organs. Notably, IL-21 inhibited Treg cell expansion in a cell intrinsic manner. Moreover, experimental augmentation of Treg cells driven by injection of IL-2/anti-IL-2 immune complexes drastically impaired the functionality of the antiviral T cell response and impeded virus clearance. As a consequence, mice became highly susceptible to chronic infection following exposure to low virus doses. These findings reveal virus-driven Treg cell proliferation as potential evasion strategy that facilitates T cell exhaustion and virus persistence. Furthermore, they suggest that besides its primary function as a direct survival signal for antiviral CD8+ T cells during chronic infections, IL-21 may also indirectly promote CD8+ T cell poly-functionality by restricting the suppressive activity of infection-induced Treg cells.en
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen
dc.titleIL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.en
dc.typeArticleen
dc.contributor.departmentMolecular Biomedicine, Institute of Molecular Health Sciences, Department of Biology, ETH Zurich, Zurich, Switzerland.en
dc.identifier.journalPLoS pathogensen

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