Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background 英文参考文献.docVIP

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Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background 英文参考文献.doc

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Regulatory T Cells Enhance Susceptibility to Experimental Trypanosoma Congolense Infection Independent of Mouse Genetic Background 英文参考文献

RegulatoryTCellsEnhanceSusceptibilityto ExperimentalTrypanosomaCongolenseInfection IndependentofMouseGeneticBackground IfeomaOkwor1,ChukwunonsoOnyilagha2,ShibyKuriakose2,ZhirongMou2,PingJia2,JudeE.Uzonna1,2* 1Department ofMedicalMicrobiology, FacultyofMedicine,UniversityofManitoba, Winnipeg,Manitoba,Canada, 2Department ofImmunology, FacultyofMedicine, UniversityofManitoba,Winnipeg,Manitoba,Canada Abstract Background: BALB/c mice are highly susceptible while C57BL/6 are relatively resistant to experimental Trypanosoma congolenseinfection.AlthoughregulatoryTcells(Tregs)havebeenshowntoregulatethepathogenesisofexperimentalT. congolenseinfection,theirexactroleremainscontroversial.WewishedtodeterminewhetherTregscontributetodistinct phenotypicoutcomesinBALB/candC57BL/6miceandifsohowtheyoperatewithrespecttocontrolofparasitemiaand productionofdisease-exacerbatingproinflammatorycytokines. Methodology/Findings:BALB/candC57BL/6micewereinfectedintraperitoneally(i.p)with103T.congolensecloneTC13 andboththekineticsofTregsexpansionandintracellularcytokineprofilesinthespleensandliversweremonitoreddirectly ex vivo by flow cytometry. In some experiments, mice were injected with anti-CD25 mAb prior or post T. congolense + infection or adoptively (by intravenous route) given highly enriched na?¨ve CD25 T lymphocytes prior to T. congolense infectionandtheinflammatorycytokine/chemokinelevelsandsurvivalweremonitored.Incontrasttoatransientandnon significantincreaseinthepercentagesandabsolutenumbersofCD4 CD25 Foxp3+Tcells(Tregs)inC57BL/6mousespleens + + andlivers,asignificantincreaseinthepercentageandabsolutenumbersofTregswasobservedinspleensofinfectedBALB/ c mice. Ablation or increasing the number of CD25 cells in the relatively resistant C57BL/6 mice by anti-CD25 mAb + + treatmentorbyadoptivetransferofCD25 Tcells,respectively,amelioratesorexacerbatesparasitemiaandproductionof proinflammatorycytokines. Conclusion: Collectively, our results show that regulatory T cells contribute