Functionally competent CD4+ T cells express high levels of T-bet in Plasmodium chabaudi infected young mice

Abstract

ABSTRACTThe immune system plays an important role in the elimination of Plasmodium parasites that cause malaria, which affect children the most worldwide. Immunity to malaria, especially in young children is poorly understood due to the absence of a developmentally-equivalent rodent model to study the pathogenesis of disease. We have developed a mouse model using 15-day old mice (pups) of malaria infection in neonatal mice. Using C57BL/6 pups, we determined that P. chabaudi infection decreases the growth rate of young mice compared to controls, and results in 60% mortality, and neurological damage not present in adults, as indicated by a battery of behavioral assays. When all splenic cells were stimulated in vitro stimulation, cells from pups proliferated faster than adult cells, but purified CD4 T cells were slower. Upon infection with Plasmodium parasites, both adult and pup CD4+ T cells were activated and differentiated to an effector T cell (Teff) phenotype; however, pup CD4+ Teff were less differentiated than adult Teff. Pup CD4+ T cells also produced more IL-2 than cells from adult B6 mice, and TNF-α was increased in parasite-specific BALB/c pup T cells. Interestingly, there were more pup CD4+T-bethi Teff after infection suggestive of increased Th1 commitment, potentially contributing to cerebral symptoms.