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dc.contributor.authorAmante, Fiona H
dc.contributor.authorStanley, Amanda C
dc.contributor.authorRandall, Louise M
dc.contributor.authorZhou, Yonghong
dc.contributor.authorHaque, Ashraful
dc.contributor.authorMcSweeney, Karli
dc.contributor.authorWaters, Andrew P
dc.contributor.authorJanse, Chris J
dc.contributor.authorGood, Michael F
dc.contributor.authorHill, Geoff R
dc.contributor.authorEngwerda, Christian R
dc.date.accessioned2017-05-03T14:54:30Z
dc.date.available2017-05-03T14:54:30Z
dc.date.issued2007
dc.date.modified2014-04-04T04:00:10Z
dc.identifier.issn0002-9440
dc.identifier.doi10.2353/ajpath.2007.061033
dc.identifier.urihttp://hdl.handle.net/10072/57884
dc.description.abstractCerebral malaria (CM) is a serious complication of Plasmodium falciparum infection that is responsible for a significant number of deaths in children and nonimmune adults. A failure to control blood parasitemia and subsequent sequestration of parasites to brain microvasculature are thought to be key events in many CM cases. Here, we show for the first time, to our knowledge, that CD4+CD25+Foxp3+ natural regulatory T (Treg) cells contribute to pathogenesis by modulating immune responses in P. berghei ANKA (PbA)-infected mice. Depletion of Treg cells with anti-CD25 monoclonal antibody protected mice from experimental CM. The accumulation of parasites in the vasculature and brain was reduced in these animals, resulting in significantly lower parasite burdens compared with control animals. Mice lacking Treg cells had increased numbers of activated CD4+ and CD8+ T cells in the spleen and lymph nodes, but CD8+ T-cell recruitment to the brain was selectively reduced in these mice. Importantly, a non-Treg-cell source of interleukin-10 was critical in preventing experimental CM. Finally, we show that therapeutic administration of anti-CD25 monoclonal antibody, even when blood parasitemia is established, can prevent disease, confirming a critical and paradoxical role for Treg cells in experimental CM pathogenesis.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Investigative Pathology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom548
dc.relation.ispartofpageto559
dc.relation.ispartofissue2
dc.relation.ispartofjournalAmerican Journal of Pathology
dc.relation.ispartofvolume171
dc.rights.retentionY
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchClinical sciences not elsewhere classified
dc.subject.fieldofresearchcode32
dc.subject.fieldofresearchcode320299
dc.titleA Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorGood, Michael F.


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