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

Haque, Ashraful, Best, Shannon E., Amante, Fiona H., Mustafah, Seri, Desbarrieres, Laure, de Labastida, Fabian, Sparwasser, Tim, Hill, Geoffrey R. and Engwerda, Christian R. (2010) CD4+ natural regulatory T Cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo. PLoS Pathogens, 6 12: 1 - e1001221-14 - e1001221. doi:10.1371/journal.ppat.1001221

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Author Haque, Ashraful
Best, Shannon E.
Amante, Fiona H.
Mustafah, Seri
Desbarrieres, Laure
de Labastida, Fabian
Sparwasser, Tim
Hill, Geoffrey R.
Engwerda, Christian R.
Title CD4+ natural regulatory T Cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
Publication date 2010-12-09
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1001221
Open Access Status DOI
Volume 6
Issue 12
Start page 1 - e1001221
End page 14 - e1001221
Total pages 14
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2011
Language eng
Formatted 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 entirelydependent 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. © 2010 Haque et al.
Keyword Cerebral Malaria
Animal cell
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 48 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 28 Mar 2011, 19:55:55 EST by Lisa Hennell on behalf of Medicine - Royal Brisbane and Women's Hospital