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CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo

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....

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Autores principales: Haque, Ashraful, Best, Shannon E., Amante, Fiona H., Mustafah, Seri, Desbarrieres, Laure, de Labastida, Fabian, Sparwasser, Tim, Hill, Geoffrey R., Engwerda, Christian R.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000360/
https://www.ncbi.nlm.nih.gov/pubmed/21170302
http://dx.doi.org/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.
author_facet Haque, Ashraful
Best, Shannon E.
Amante, Fiona H.
Mustafah, Seri
Desbarrieres, Laure
de Labastida, Fabian
Sparwasser, Tim
Hill, Geoffrey R.
Engwerda, Christian R.
author_sort Haque, Ashraful
collection PubMed
description 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.
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spelling pubmed-30003602010-12-17 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. Engwerda, Christian R. PLoS Pathog Research Article 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. Public Library of Science 2010-12-09 /pmc/articles/PMC3000360/ /pubmed/21170302 http://dx.doi.org/10.1371/journal.ppat.1001221 Text en Haque et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Haque, Ashraful
Best, Shannon E.
Amante, Fiona H.
Mustafah, Seri
Desbarrieres, Laure
de Labastida, Fabian
Sparwasser, Tim
Hill, Geoffrey R.
Engwerda, Christian R.
CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title_full CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title_fullStr CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title_full_unstemmed CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title_short CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
title_sort cd4(+) natural regulatory t cells prevent experimental cerebral malaria via ctla-4 when expanded in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000360/
https://www.ncbi.nlm.nih.gov/pubmed/21170302
http://dx.doi.org/10.1371/journal.ppat.1001221
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