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....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3000360?pdf=render |
| _version_ | 1828756638428823552 |
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| author | Ashraful Haque Shannon E Best Fiona H Amante Seri Mustafah Laure Desbarrieres Fabian de Labastida Tim Sparwasser Geoffrey R Hill Christian R Engwerda |
| author_facet | Ashraful Haque Shannon E Best Fiona H Amante Seri Mustafah Laure Desbarrieres Fabian de Labastida Tim Sparwasser Geoffrey R Hill Christian R Engwerda |
| author_sort | Ashraful Haque |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T23:20:34Z |
| format | Article |
| id | doaj.art-0bc03bb710e84f59aad5adc95adbcf44 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T23:20:34Z |
| publishDate | 2010-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0bc03bb710e84f59aad5adc95adbcf442022-12-22T01:29:44ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-01-01612e100122110.1371/journal.ppat.1001221CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.Ashraful HaqueShannon E BestFiona H AmanteSeri MustafahLaure DesbarrieresFabian de LabastidaTim SparwasserGeoffrey R HillChristian R EngwerdaStudies 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.http://europepmc.org/articles/PMC3000360?pdf=render |
| spellingShingle | Ashraful Haque Shannon E Best Fiona H Amante Seri Mustafah Laure Desbarrieres Fabian de Labastida Tim Sparwasser Geoffrey R Hill Christian R Engwerda CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo. PLoS Pathogens |
| 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 |
| url | http://europepmc.org/articles/PMC3000360?pdf=render |
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