IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.
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....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3656089?pdf=render |
| _version_ | 1818486158874640384 |
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| author | Iwana Schmitz Christoph Schneider Anja Fröhlich Helge Frebel Daniel Christ Warren J Leonard Tim Sparwasser Annette Oxenius Stefan Freigang Manfred Kopf |
| author_facet | Iwana Schmitz Christoph Schneider Anja Fröhlich Helge Frebel Daniel Christ Warren J Leonard Tim Sparwasser Annette Oxenius Stefan Freigang Manfred Kopf |
| author_sort | Iwana Schmitz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T16:19:09Z |
| format | Article |
| id | doaj.art-84e38bde11d04349a209e868f20ad57f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T16:19:09Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-84e38bde11d04349a209e868f20ad57f2022-12-22T01:41:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0195e100336210.1371/journal.ppat.1003362IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.Iwana SchmitzChristoph SchneiderAnja FröhlichHelge FrebelDaniel ChristWarren J LeonardTim SparwasserAnnette OxeniusStefan FreigangManfred KopfFoxp3+ 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.http://europepmc.org/articles/PMC3656089?pdf=render |
| spellingShingle | Iwana Schmitz Christoph Schneider Anja Fröhlich Helge Frebel Daniel Christ Warren J Leonard Tim Sparwasser Annette Oxenius Stefan Freigang Manfred Kopf IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. PLoS Pathogens |
| title | IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. |
| title_full | IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. |
| title_fullStr | IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. |
| title_full_unstemmed | IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. |
| title_short | IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection. |
| title_sort | il 21 restricts virus driven treg cell expansion in chronic lcmv infection |
| url | http://europepmc.org/articles/PMC3656089?pdf=render |
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