title: Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection.
abstract: OBJECTIVE
  HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation.
  
  
  METHODS
  Peripheral and cord blood mononuclear cells (PBMCs; CBMC) from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs) were measured.
  
  
  RESULTS
  CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low) and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs.
  
  
  CONCLUSIONS
  The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis.
authors.affiliation: The Kirby Institute, The University of New South Wales, Sydney, Australia. s.sasson@amr.org.au
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Sasson
authors.forename: John J
authors.initials: JJ
authors.lastname: Zaunders
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
authors.forename: Michelle
authors.initials: M
authors.lastname: Bailey
authors.forename: Kristin
authors.initials: K
authors.lastname: McBride
authors.forename: Kersten K
authors.initials: KK
authors.lastname: Koelsch
authors.forename: Kate M
authors.initials: KM
authors.lastname: Merlin
authors.forename: Don E
authors.initials: DE
authors.lastname: Smith
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
mesh_terms: D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002470:Cell Survival; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology*; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D013950:Thymus Gland / Q000276:immunology*
chemical_list: C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D053699:Interleukin-7 Receptor alpha Subunit