Magnitude of stimulation dictates the cannabinoid‐mediated differential T cell response to HIVgp120

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

关键词: immunomodulation;    cytotoxic T lymphocytes;    antigen specificity;    cytokines;    NFAT‐;    calcium signaling;   

DOI  :  10.1189/jlb.0212082

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Approximately25%ofimmunocompromisedHIVpatientssmokemarijuanaforitsputativetherapeuticbenefit.Thegoalofthesestudieswastotestthehypothesisthatmarijuana‐derivedcannabinoidshaveimmunomodulatoryeffectsonHIVantigen‐specificTcelleffectorfunction.AsurrogatemousemodeltoinducepolyclonalTcellresponsesagainstHIVgp120wasestablished.THC,amarijuana‐derivedcannabinoid,suppressedorenhancedmouseCD8+Tcellproliferationandthegp120‐specificCTLresponsedependingonthemagnitudeoftheIFN‐γresponse.TodeterminethemolecularmechanismsbywhichcannabinoidsdifferentiallymodulateTcellresponses,P/Ioranti‐CD3/CD28antibodieswereusedforstimulation,andanothermarijuana‐derivedcannabinoid,CBD,wasalsoinvestigated.THCorCBDsuppressedorenhancedIFN‐γandIL‐2productionbymousesplenocytesunderoptimalorsuboptimalstimulation,respectively.SimilardifferentialeffectsofcannabinoidsoncytokineproductionwerealsoobservedonnucleartranslocationofNFATandwithhumanPBMCsinresponsetoP/Istimulation.However,THCandCBDelevatedintracellularcalcium,regardlessofthestimulationlevelwithP/I,suggestingthatthecannabinoid‐inducedcalciumincreaseprovidesanappropriatesignalforactivationinsuboptimallystimulatedTcellsbutananergic‐likesignalasaresultofexcessivecalciuminoptimallystimulatedTcells.Overall,thesedatademonstratedifferentialmodulationbycannabinoidsofaHIVantigen‐specificresponseandidentifyapossiblemechanismresponsibleforthiseffect...

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