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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....
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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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. |
format | Text |
id | pubmed-3000360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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