CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo |
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Authors: | 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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Affiliation: | Immunology and Infection Laboratory, Queensland Institute of Medical Research and The Australian Centre for Vaccine Development, Herston, Brisbane, Queensland, Australia. ashraful.haque@qimr.edu.au |
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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. |
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