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CD4+ T-cell derived IL-10 mitigates malarial anemia




Kiser, Patti, author
Avery, Anne, advisor
Callan, Robert, committee member
Olver, Christine, committee member
Quackenbush, Sandra, committee member

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Individuals living in malaria endemic areas develop effective anti-parasite immunity over several years of repeated exposure, but become resistant to severe disease after just one or two infections. This observation suggests that the acquired immune system plays a role in both processes, but may involve different mechanisms. Using the mouse model of malaria caused by non-lethal Plasmodium yoelii, we test the hypothesis that CD4+ T-cell derived IL-10 contributes to disease resistance by mitigating severe anemia. Here we show that IL-10 deficient mice develop significant anemia despite a very low parasite burden. Anemia in this model is mediated primarily by increased erythrocyte destruction and not from suppressed erythropoiesis. Wild type mice that have recovered from P. yoelii infection have an expanded population of IL-10 producing CD4 T cells, with the majority of these cells co-expressing IFN-γ and display a Th1 phenotype. In the absence of IL-10, there is an increase in IFN-γ+ T cells. We demonstrate that IL-10 competent CD4+ T cells protect athymic nude mice from anemia when compared to CD4 T cells taken from recovered IL-10 deficient mice. Utilizing an ex vivo system that tests the function of APCs in activating CD4+ T-cells, we also determined that APCs exposed to P. yoelii in vivo induced a greater population of CD4+ T-cells that express IL-10 compared to naïve APCs. We also demonstrate that IFN-γ is required, with the possible involvement of IL-10 and IL-12, for efficient IL-10 expression in CD4+ T-cells. Our findings suggest that one mechanism by which the acquired immune system contributes to resistance to severe anemia may be the development of CD4 T cells that co-express IL-10 and IFN-γ, thereby self-regulating IFN-γ levels, which then inhibits pro-inflammatory mediated destruction of naïve red blood cells.


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immune mediated


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