CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10033/550487
Title:
CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.
Authors:
Haque, Ashraful; Best, Shannon E; Amante, Fiona H; Mustafah, Seri; Desbarrieres, Laure; de Labastida, Fabian; Sparwasser, Tim; Hill, Geoffrey R; Engwerda, Christian R
Abstract:
Studies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not improve parasite control or disease outcome. In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease. This protection was entirely dependent upon Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain. Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA-4 but not IL-10. These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.
Citation:
CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo. 2010, 6 (12):e1001221 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
2010
URI:
http://hdl.handle.net/10033/550487
DOI:
10.1371/journal.ppat.1001221
PubMed ID:
21170302
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.authorHaque, Ashrafulen
dc.contributor.authorBest, Shannon Een
dc.contributor.authorAmante, Fiona Hen
dc.contributor.authorMustafah, Serien
dc.contributor.authorDesbarrieres, Laureen
dc.contributor.authorde Labastida, Fabianen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorHill, Geoffrey Ren
dc.contributor.authorEngwerda, Christian Ren
dc.date.accessioned2015-04-23T08:56:44Zen
dc.date.available2015-04-23T08:56:44Zen
dc.date.issued2010en
dc.identifier.citationCD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo. 2010, 6 (12):e1001221 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid21170302en
dc.identifier.doi10.1371/journal.ppat.1001221en
dc.identifier.urihttp://hdl.handle.net/10033/550487en
dc.description.abstractStudies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not improve parasite control or disease outcome. In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease. This protection was entirely dependent upon Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain. Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA-4 but not IL-10. These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntigens, CDen
dc.subject.meshCD4-Positive T-Lymphocytesen
dc.subject.meshCD8-Positive T-Lymphocytesen
dc.subject.meshCTLA-4 Antigenen
dc.subject.meshCell Proliferationen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshInterleukin-10en
dc.subject.meshMalaria, Cerebralen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshPlasmodium bergheien
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleCD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.en
dc.typeArticleen
dc.identifier.journalPLoS pathogensen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.