CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo
AuthorHaque, A; Best, SE; Amante, FH; Mustafah, S; Desbarrieres, L; de Labastida, F; Sparwasser, T; Hill, GR; Engwerda, CR
Source TitlePLoS Pathogens
PublisherPUBLIC LIBRARY SCIENCE
University of Melbourne Author/sHaque, Ashraful
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsHaque, A., Best, S. E., Amante, F. H., Mustafah, S., Desbarrieres, L., de Labastida, F., Sparwasser, T., Hill, G. R. & Engwerda, C. R. (2010). CD4(+) Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo. PLOS PATHOGENS, 6 (12), https://doi.org/10.1371/journal.ppat.1001221.
Access StatusOpen Access
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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