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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
Haque, Ashraful
Best, Shannon E
Amante, Fiona H
Mustafah, Seri
Desbarrieres, Laure
de Labastida, Fabian
Sparwasser, Tim
Hill, Geoffrey R
Engwerda, Christian R
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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.
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Article
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en
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1553-7374