Cd4+ natural regulatory t cells prevent experimental cerebral malaria via CTLA-4 when expanded in vivo

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 entirelydependent 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. © 2010 haque et al.