Regulatory T Cells in Human Lymphatic Filariasis Stronger Functional Activity in Microfilaremics 英文参考文献.docVIP

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Regulatory T Cells in Human Lymphatic Filariasis Stronger Functional Activity in Microfilaremics 英文参考文献.doc

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Regulatory T Cells in Human Lymphatic Filariasis Stronger Functional Activity in Microfilaremics 英文参考文献

RegulatoryTCellsinHumanLymphaticFilariasis: StrongerFunctionalActivityinMicrofilaremics LindaJ.Wammes1,2*,FirdausHamid1,3,ApriliantoE.Wiria1,2,HeriWibowo2,ErliyaniSartono1, RickM.Maizels4,HermelijnH.Smits1,TaniawatiSupali2,MariaYazdanbakhsh1* 1Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands, 2Department of Parasitology, University of Indonesia, Jakarta, Indonesia, 3DepartmentofMicrobiology,HasanuddinUniversity,Makassar,Indonesia,4InstituteofImmunologyandInfectionResearch,UniversityofEdinburgh,Edinburgh,United Kingdom Abstract InfectionwithfilarialparasitesisassociatedwithTcellhyporesponsiveness,whichisthoughttobepartlymediatedbytheir abilitytoinduceregulatoryTcells(Tregs)duringhumaninfections.ThisstudyinvestigatesthefunctionalcapacityofTregs fromdifferentgroupsoffilarialpatientstosuppressfilaria-specificimmuneresponsesduringhumanfilariasis.Microfilaremic (MF),chronicpathology(CP)anduninfectedendemicnormal(EN)individualswereselectedinanareaendemicforBrugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25hi cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg- depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responseswerelowercomparedtoENandCPgroups.DepletionofTregsrestoredTcellaswellasBcellproliferationinMF- positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressingproliferationandpossiblyTh2cytokineresponsestoBmA.Thesesuppressiveeffectswereonlyobservedinthe MFgroupandnotinENorCP.Thesefindingsmaybeimportantwhenconsideringstrategiesforfilarialtreatmentandthe targetedpreventionoffilaria-inducedlymphedema. Citation:WammesLJ,HamidF,WiriaAE,WibowoH,SartonoE,