title: The number of CCR5 expressing CD4+ T lymphocytes is lower in HIV-infected long-term non-progressors with viral control compared to normal progressors: a cross-sectional study.
abstract: BACKGROUND
  The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV.
  
  
  METHODS
  In this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 > 750 cell/μl & HIV < 50 copies for ≥2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands. We determined the CCR5 and CXCR4 expression among CD4(+) and CD8(+) lymphocyte subsets; memory (CD45RO(+)), naïve (CD45RA(+)) cells and regulatory T-cells (CD4(+)CD25(high)FoxP3(+)). In addition, CCR5∆32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction.
  
  
  RESULTS
  The percentage of CCR5-expressing CD4(+) cells of LTNP was comparable with healthy controls; whereas HIV-infected individuals showed more CCR5-expressing cells. This was observed in memory and naïve CD4(+) cells, but not in regulatory T-cells. The mean fluorescence intensity of CCR5-expressing CD4(+) cells was similar in all groups. All groups had comparable percentages of CXCR4-expressing cells. The mean fluorescence intensity of CXCR4-expressing cells was significantly higher in HIV-infected normally progressors in both memory and naïve CD4(+) cells, but not in CD8(+) cells. The CCR5∆32 polymorphism was not related to group.
  
  
  CONCLUSIONS
  We show that HIV affects -directly or indirectly- the expression of CCR5 in CD4(+) T-lymphocytes; yet this effect is not seen in LTNP with viral control. Avoiding upregulation of CCR5 could be an important method via which LTNP counteracts the effects of HIV and suppresses viral replication. Exploring how LTNP suppress the upregulation of CCR5 could be an important step for discovering new therapeutics.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Route 456, PO Box 910, 6500 HB, Nijmegen, The Netherlands. Hinta.Meijerink@fhi.no.
authors.forename: Hinta
authors.initials: H
authors.lastname: Meijerink
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia. agnesariantana_sppk@yahoo.co.id.
authors.forename: Agnes R
authors.initials: AR
authors.lastname: Indrati
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Route 456, PO Box 910, 6500 HB, Nijmegen, The Netherlands. Reinout.vanCrevel@radboudumc.nl.
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.affiliation: Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Irma.Joosten@radboudumc.nl.
authors.forename: Irma
authors.initials: I
authors.lastname: Joosten
authors.affiliation: Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Hans.Koenen@radboudumc.nl.
authors.forename: Hans
authors.initials: H
authors.lastname: Koenen
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Route 456, PO Box 910, 6500 HB, Nijmegen, The Netherlands. Andre.vanderVen@radboudumc.nl.
authors.forename: Andre J A M
authors.initials: AJ
authors.lastname: van der Ven
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D019713:Receptors, CCR5 / Q000276:immunology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C584933:CCR5 protein, human; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4