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

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dc.contributor.authorKiser, Patti, author
dc.contributor.authorAvery, Anne, advisor
dc.contributor.authorCallan, Robert, committee member
dc.contributor.authorOlver, Christine, committee member
dc.contributor.authorQuackenbush, Sandra, committee member
dc.date.accessioned2007-01-03T06:08:49Z
dc.date.available2007-01-03T06:08:49Z
dc.date.issued2013
dc.description.abstractIndividuals 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.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierKiser_colostate_0053A_12015.pdf
dc.identifierETDF2013500309MIPA
dc.identifier.urihttp://hdl.handle.net/10217/80953
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectanemia
dc.subjectT-cells
dc.subjectmalaria
dc.subjectimmune mediated
dc.titleCD4+ T-cell derived IL-10 mitigates malarial anemia
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineMicrobiology, Immunology, and Pathology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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