Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points.

2.50
Hdl Handle:
http://hdl.handle.net/10033/593749
Title:
Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points.
Authors:
Dietze, Kirsten K; Zelinskyy, Gennadiy; Gibbert, Kathrin; Schimmer, Simone; Francois, Sandra; Myers, Lara; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Hasenkrug, Kim J; Dittmer, Ulf
Abstract:
Although chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8(+) T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8(+) T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.
Affiliation:
TWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.
Citation:
Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. 2011, 108 (6):2420-5 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
8-Feb-2011
URI:
http://hdl.handle.net/10033/593749
DOI:
10.1073/pnas.1015148108
PubMed ID:
21262821
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorDietze, Kirsten Ken
dc.contributor.authorZelinskyy, Gennadiyen
dc.contributor.authorGibbert, Kathrinen
dc.contributor.authorSchimmer, Simoneen
dc.contributor.authorFrancois, Sandraen
dc.contributor.authorMyers, Laraen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHasenkrug, Kim Jen
dc.contributor.authorDittmer, Ulfen
dc.date.accessioned2016-01-18T14:55:33Zen
dc.date.available2016-01-18T14:55:33Zen
dc.date.issued2011-02-08en
dc.identifier.citationTransient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. 2011, 108 (6):2420-5 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490en
dc.identifier.pmid21262821en
dc.identifier.doi10.1073/pnas.1015148108en
dc.identifier.urihttp://hdl.handle.net/10033/593749en
dc.description.abstractAlthough chronic infections with viruses such as HIV and hepatitis C virus have been associated with regulatory T cell (Treg)-mediated suppression of virus-specific CD8(+) T-cell activity, no causal relationship between Tregs and chronic viral set points has been established. Using transgenic mice in which Tregs can be selectively ablated, we now show that transient depletion of Tregs during a chronic retroviral infection allows exhausted CD8(+) T cells to regain antiviral functions, including secretion of cytokines, production of cytotoxic molecules, and virus-specific cytolytic activity. Furthermore, short-term Treg ablation resulted in long-term reductions in chronic virus loads. These results demonstrate that Treg-mediated immunosuppression can be a significant factor in the maintenance of chronic viral infections and that Treg-targeted immunotherapy could be a valuable component in therapeutic strategies to treat chronic infectious diseases.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCD8-Positive T-Lymphocytesen
dc.subject.meshChronic Diseaseen
dc.subject.meshCytokinesen
dc.subject.meshLymphocyte Depletionen
dc.subject.meshMiceen
dc.subject.meshMice, Transgenicen
dc.subject.meshRetroviridae Infectionsen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleTransient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Centre for Experimental and Clinical Infection Research GmbH, Feodor-Lynen-Str. 3-7, 30625 Hannover, Germany.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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