CD4+ natural regulatory T cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo.

• Main Authors: Ashraful Haque, Shannon E Best, Fiona H Amante, Seri Mustafah, Laure Desbarrieres, Fabian de Labastida, Tim Sparwasser, Geoffrey R Hill, Christian R Engwerda
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-01-01
• Series: PLoS Pathogens
• Online Access: http://europepmc.org/articles/PMC3000360?pdf=render
• ISSN: 1553-7366; 1553-7374

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.