Splenocytes from young mice protect immunocompromised mice against death from malaria infection, but they do not proliferate well.

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Abstract The immune system plays an essential role in the elimination of malaria parasites. CD4+ T cells are imperative in the immune response to the infection, but immune response to malaria especially in young children is poorly understood, due to a lack of a better young animal model to study the pathogenesis of the disease. We have developed a young mouse (pup) model using day 15 pups to help understand the pathogenesis, and development of protective CD4 T cells in malaria infection. Here, we determined the ability of pup cells to protect immunocompromised RAGKO mice from malaria infection. We infected day 15 old pups with Plasmodium chabudi at 1×105 iRBCs, and transferred splenocytes to RAGKO mice on day 8 post-infection. RAGKO mice were then infected. Mice that received pup cells looked healthier and active throughout the experiment, compared to their counterparts who received adult spleen cells. During the peak of infection, mice that received adult cells lost more weight than the pup cell recipients. On day 60 post-transfer, we observed same numbers of CD4 T cells, central memory and effector memory T cells. There were significantly lower proportions and numbers of IFNγ and TNFα positive cells from pups compared to adult cells. We next determined if there was any difference in the proliferation of CD4 T cells and all splenocytes in pup cells. We purified CD4+ T cells using EasySep kit and cultured them on αCD3/CD28 pre-coated plates, compared to all splenocytes. There was a significant growth in purified CD4 T cells from adult than pup cells. Interestingly, all splenocytes from pups proliferated better than adults. Therefore, our data suggest that pup cells protect RAGKO mice from death, but do not develop into functional memory due to poor proliferation.