Adenosine deaminase regulates Treg expression in autologous T cell‐dendritic cell cocultures from patients infected with HIV‐1

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: AIDS;    chemokine;    RANTES;    memory cells;    vaccine;   

DOI  :  10.1189/jlb.3A1214-580RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

RegulatoryTcellshaveanimportantroleinimmunesuppressionduringHIV‐1infection.AsregulatoryTcellsproducetheimmunomodulatorymoleculeadenosine,ouraimherewastoassessthepotentialofadenosineremovaltorevertthesuppressionofanti‐HIVresponsesexertedbyregulatoryTcells.TheexperimentalsetupconsistedofexvivococulturesofTanddendriticcells,towhichadenosinedeaminase,anenzymethathydrolyzesadenosine,wasadded.Incellsfromhealthyindividuals,adenosinehydrolysisdecreasedCD4+CD25hiregulatoryTcells.Additionof5′‐N‐ethylcarboxamidoadenosine,anadenosinereceptoragonist,significantlydecreasedCD4+CD25locells,confirmingamodulatoryroleofadenosineactingviaadenosinereceptors.InautologouscoculturesofTcellswithHIV‐1‐pulseddendriticcells,additionofadenosinedeaminaseledtoasignificantdecreaseofHIV‐1‐inducedCD4+CD25hiforkheadboxp3+cellsandtoasignificantenhancementoftheHIV‐1‐specificCD4+responderTcells.AnincreaseintheeffectorresponsewasconfirmedbytheenhancedproductionofCD4+andCD8+CD25−CD45RO+memorycellgenerationandsecretionofTh1cytokines,includingIFN‐γandIL‐15andchemokinesMIP‐1α/CCL3,MIP‐1β/CCL4,andRANTES/CCL5.Theseexvivoresultsshow,inaphysiologicallyrelevantmodel,thatadenosinedeaminaseisabletoenhanceHIV‐1effectorresponsesmarkedly.ThepossibilitytorevertregulatoryTcell‐mediatedinhibitionofimmuneresponsesbyuseofadenosinedeaminase,anenzymethathydrolyzesadenosine,meritsattentionforrestoringTlymphocytefunctioninHIV‐1infection...

【 授权许可】

CC BY