Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti‐HIV CD8+ T cell function in vitro

[摘要] HIVinfectionisassociatedwithelevatedexpressionofIL‐10andPD‐L1,contributingtoimpairmentofTcelleffectorfunctions.Inautoimmunity,tumorimmunology,andsomeviralinfections,BregsmodulateTcellfunctionviaIL‐10production.Inthisstudy,wetestedthehypothesisthatduringHIVinfection,BregsattenuateCD8+Tcelleffectorfunction,contributingtoimmunedysfunction.Wedeterminedthatinvitro,TLR2‐,TLR9‐,andCD40L‐costimulatedBregsfromHIV−individualsexhibitedahighfrequencyofcellsexpressingIL‐10andPD‐L1.ComparedwithBregsfromHIV−individuals,asignificantlyhigherpercentageofBregsfromHIV+individualsspontaneouslyexpressedIL‐10(P=0.0218).AfterinvitrostimulationwithHIVpeptides,Breg‐depletedPBMCsfromHIV+individualsexhibitedaheightenedfrequencyofcytotoxic(CD107a+;P=0.0171)andHIV‐specificCD8+TcellscomparedwithtotalPBMCs.Furthermore,BregdepletionledtoenhancedproliferationoftotalCD8+andCD107a+CD8+Tcells(P=0.0280,andP=0.0102,respectively).Inaddition,augmentedCD8+Tcelleffectorfunctioninvitrowasreflectedina67%increasedclearanceofinfectedCD4+Tcells.TheobservedBregsuppressionofCD8+TcellproliferationwasIL‐10‐dependent.InHIV+individuals,Bregfrequencycorrelatedpositivelywithviralload(r=0.4324;P=0.0095),immuneactivation(r=0.5978;P=0.0005),andCD8+Tcellexhaustion(CD8+PD‐1+;r=0.5893;P=0.0101).Finally,thefrequencyofPD‐L1‐expressingBregscorrelatedpositivelywithCD8+PD‐1+Tcells(r=0.4791;P=0.0443).OurdataindicatethatBregscontributetoHIV‐infectionassociatedimmunedysfunctionbyTcellimpairment,viaIL‐10andpossiblyPD‐L1expression...

[学科分类] 生理学

[关键词] immune activation;immune exhaustion;IL‐10