Gamma Delta and Natural Killer cells in Splenocytes of Young mice Protect Immunocompromised mice from Death in Plasmodium chabaudi Infection

Abstract Immunity to malaria requires an elongated time to develop and understanding of the immune response to malaria, especially in children under five, is limited due to the lack of a reliable animal model to study the pathogenesis of the disease. By utilizing a newly developed young rodent model in our lab, we have observed that purified CD4+ T cells from 8-week adult mice proliferate faster than day 15 old young mice (pups) when stimulated in vitro. Surprisingly, we observed faster proliferation of splenocytes in the pups, when compared to the cells from adult mice. When transferred to immunocompromised RAGKO mice, both pup and adult cells protected from death. These data suggest that apart from CD4+ T cells, there is a faster responsive cell population in the pups that may promote protection against malaria infection in mice. To better understand this responsive cell population in young mice, we adoptively transferred splenocytes from both adults and pups into immunocompromised RAGKO mice and infected these cell recipients with P. chabaudi. We observed higher proportions and numbers of gamma delta (gd) T cells in the pup splenocyte recipients when compared to adult counterparts on day 8 post-infection. Interestingly, we observed lower proportions and numbers of natural killer (NK) cells in the adult cell recipients compared to pup recipients. However, there were significantly higher proportions, but not numbers of macrophages in the adult cell recipients. Taken together, our findings suggest that pup cells are enriched or promote an innate immune response comprising of gd and NK cells, while adult cells inhibit the expansion of these innate lymphocyte cells in malaria infection.