Age-Related Differences in Naturally Acquired T Cell Memory to Plasmodium falciparum Merozoite Surface Protein 1 英文参考文献.docVIP

Age-RelatedDifferencesinNaturallyAcquiredTCell MemorytoPlasmodiumfalciparumMerozoiteSurface Protein1 KiprotichChelimo1,3,PaulaB.Embury2,PeterOdadaSumba1,JohnVulule1,AyubV.Ofulla3 ,Carole Long4,JamesW.Kazura2,AnnM.Moormann2,5* 1Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya, 2Center for Global Health and Diseases, Case Western Reserve University, Cleveland,Ohio,UnitedStatesofAmerica,3MasenoUniversity,Maseno,Kenya,4LaboratoryofMalariaandVectorResearch,NationalInstituteofAllergyandInfectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America, 5Department of Pediatrics and Department of Quantitative Health Sciences, UniversityofMassachusettsMedicalSchool,Worcester,Massachusetts,UnitedStatesofAmerica Abstract Naturally acquired immunity to Plasmodium falciparum malaria in malaria holoendemic areas is characterized by the gradual,age-relateddevelopmentofprotectionagainsthigh-densityparasitemiaandclinicalmalaria.Animalstudies,and lesscommonly,observationsofhumanswithmalaria,suggestthatT-cellresponsesareimportantinthedevelopmentand maintenanceofthisimmunity,whichismediatedprimarilybyantibodiesthatslowrepeatedcyclesofmerozoitesthrough erythrocytes. To advance our rather limited knowledge on human T-cell immunity to blood stage malaria infection, we evaluatedCD4andCD8T-celleffectormemorysubsetresponsestothe42kDaC-terminalfragmentofMerozoiteSurface Protein 1 (MSP142), a malaria vaccine candidate, by 49 healthy 0.5 to $18 year old residents of a holoendemic area in western Kenya. The proportion of individuals with peripheral blood mononuclear cell MSP142 driven IFN-c ELISPOT responsesincreasedfrom20%(2/20)among0.5–1yearoldchildrento90%(9/10)ofadults$18years(P=0.01);parallel increasesinthemagnitudeofIFN-cresponseswereobservedacrossallagegroups(0.5,1,2,5and$18years,P =0.001). Lessthan1%oftotalCD4andCD8T-cellsfrombothchildrenandadultsproducedIFN-cinresponsetoMSP142 .However, adultshadhigherproportionsofMSP1