title: CD4⁺ recent thymic emigrants are infected by HIV in vivo, implication for pathogenesis.
abstract: OBJECTIVE
  The contribution of naive CD4⁺ T cells to the pool of HIV-infected cells remains poorly described. This study aimed at evaluating HIV infection in naive T-cell subsets in viremic and HAART-treated patients, together with various parameters implicated in naive T-cell homeostasis, in order to better understand infection in these subsets.
  
  
  METHODS
  HIV provirus was quantified in various FACS-sorted CD4/CD8 T-cell subsets [recent thymic emigrants (RTEs), non-RTE naives and memory T cells] purified from peripheral blood cells of untreated viremic and HAART-treated aviremic HIV-infected patients. HIV proviral DNA was quantified using a highly sensitive real-time PCR assay allowing detection of one HIV copy in 10⁵ cells. Intrathymic precursor T-cell proliferation and circulating T-cell cycling were, respectively, evaluated through measurement of the sj/βTREC ratio (signal joint T-Cell Receptor Excision Circle frequency divided by DβJβTREC frequency) and Ki-67 expression. Plasma interleukin (IL)-7 concentrations were measured by ELISA.
  
  
  RESULTS
  RTEs and non-RTEs were equally HIV infected. Altogether, naive CD4⁺ T cells represented 0.24%-60% of the infected cells. In contrast, HIV DNA was undetectable in naive CD8⁺ T cells. RTE infection rate directly correlated with IL-7 plasma levels (r = 0.607, P = 0.0035) but was independent from plasma viral load, peripheral T-cell cycling and intrathymic precursor T-cell proliferation.
  
  
  CONCLUSIONS
  We demonstrated that RTEs are effectively HIV infected. The similar infection rate observed in RTEs and other naive T cells, its relationship with plasma IL-7 levels, together with the lack of correlation between RTE infection and either thymic or peripheral proliferation, strongly suggests that RTE infection occurs either late during thymopoiesis or early on during their extrathymic maturation.
authors.affiliation: Institut Cochin, Département Immunologie-Hematologie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Fabre-Mersseman
authors.forename: Jacques
authors.initials: J
authors.lastname: Dutrieux
authors.forename: Anne
authors.initials: A
authors.lastname: Louise
authors.forename: Sandra
authors.initials: S
authors.lastname: Rozlan
authors.forename: Aurélia
authors.initials: A
authors.lastname: Lamine
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Parker
authors.forename: Magali
authors.initials: M
authors.lastname: Rancez
authors.forename: Helena
authors.initials: H
authors.lastname: Nunes-Cabaço
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Rémi
authors.initials: R
authors.lastname: Cheynier
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes; D004279:DNA, Viral / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D015851:Interleukin-7; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D013950:Thymus Gland / Q000276:immunology* / Q000821:virology; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D015851:Interleukin-7