Progressive Activation of CD127+132? Recent Thymic Emigrants into Terminally Differentiated CD127?132+ T-Cells in HIV-1 Infection 英文参考文献.docVIP
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ProgressiveActivationofCD127132?RecentThymicEmigrantsintoTerminallyDifferentiatedCD127?132T-CellsinHIV-1Infection英文参考文献
ProgressiveActivationofCD127+1322RecentThymic
EmigrantsintoTerminallyDifferentiatedCD1272132+
T-CellsinHIV-1Infection
SarahC.Sasson1,2*,JohnJ.Zaunders2,NabilaSeddiki1,2,MichelleBailey1,2,KristinMcBride1,2,KerstenK.
Koelsch1,2,KateM.Merlin2,DonE.Smith1,DavidA.Cooper1,2,AnthonyD.Kelleher1,2
1TheKirbyInstitute,TheUniversityofNewSouthWales,Sydney,Australia,2HIVImmunopathologyResearchLaboratory,StVincent’sHospitalCentreforAppliedMedical
Research,Sydney,Australia
Abstract
Aim:HIVinfectionisassociatedwithdistortionofT-cellhomeostasisandtheIL-7/IL7Raxis.Progressiveinfectionresultsin
lossofCD127+1322andgainsinCD1272132+CD4+andCD8+T-cells.WeinvestigatedthecorrelatesoflossofCD127
fromtheT-cellsurfacetounderstandmechanismsunderlyingthishomeostaticdysregulation.
Methods:Peripheralandcordbloodmononuclearcells(PBMCs;CBMC)fromhealthyvolunteersandPBMCfrompatients
with HIV infection were studied. CD127+1322, CD127+132+ and CD1272132+ T-cells were phenotyped by activation,
differentiation,proliferationandsurvivalmarkers.CellularHIV-DNAcontentandsignal-jointT-cellreceptorexcisioncircles
(sjTRECs)weremeasured.
Results:CD127+1322T-cellswereenrichedforna?¨vecellswhileCD1272132+T-cellswereenrichedforactivated/terminally
differentiatedT-cellsinCD4+andCD8+subsetsinhealthandHIVinfection.HIVwasassociatedwithincreasedproportions
ofactivated/terminallydifferentiatedCD1272132+T-cells.IncontrasttoCD127+1322T-cells,CD1272132+T-cellswereKi-
67+Bcl-2
sjTRECs.
low
and contained increased levels of HIV-DNA. Na?¨ve CD127+1322 T-cells contained a higher proportion of
Conclusion:ThelossofCD127fromtheT-cellsurfaceinHIVinfectionisdrivenbyactivationofCD127+1322recentthymic
emigrants into CD1272132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of
CD127andpermanentdistortionofT-cellhomeostasis.
Citation:SassonSC,ZaundersJJ,SeddikiN,BaileyM,McBrideK,etal.(2012)ProgressiveActivationofCD127+1322RecentThymicEmigrantsintoTerminally
DifferentiatedCD1272132+T-Cellsi
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