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

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

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Studies in malaria patients Stereo Headphones 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 Sugar Bowls can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.