title: Different immunological phenotypes associated with preserved CD4+ T cell counts in HIV-infected controllers and viremic long term non-progressors.
abstract: BACKGROUND
  HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell counts in controllers and LTNP.
  
  
  METHODS
  25 HIV-infected controllers and 14 LTNP were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Production and destruction of T cells were addressed by determination of T cell receptor excision circles (TREC), recent thymic emigrants, naïve cells, immune activation, senescence and apoptosis. Furthermore, telomere length was determined, and the amount of lymphoid tissue in tonsil biopsies was quantified.
  
  
  RESULTS
  Controllers presented with partly preserved thymic output, preserved expression of the IL-7 receptor and IL-7 receptor density, and lower levels of destruction of cells than progressors resembling HIV-negative healthy controls. In contrast, LTNP appeared much like progressors, and different from controllers in immune activation, senescence, and apoptosis. Interestingly, CD8+ RTE, TREC and telomere length were partly preserved. Finally, both controllers and LTNP displayed decreased amounts of lymphoid tissue compared to healthy controls.
  
  
  CONCLUSIONS
  Controllers presented with an immunological profile different from LTNP. While controllers resembled healthy controls, LTNP were similar to progressors, suggesting different immunological mechanisms to be responsible for preserved CD4+ T cell counts in LTNP and controllers. However, both controllers and LTNP presented with reduced amounts of lymphoid tissue despite preserved CD4+ T cell counts, indicating HIV to cause damage even in non-progressors.
authors.affiliation: Viro-immunology Research Group, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Julie Christine
authors.initials: JC
authors.lastname: Gaardbo
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hartling
authors.forename: Andreas
authors.initials: A
authors.lastname: Ronit
authors.forename: Kristina
authors.initials: K
authors.lastname: Thorsteinsson
authors.forename: Hans Ole
authors.initials: HO
authors.lastname: Madsen
authors.forename: Karoline
authors.initials: K
authors.lastname: Springborg
authors.forename: Lise Mette Rahbek
authors.initials: LM
authors.lastname: Gjerdrum
authors.forename: Carsten
authors.initials: C
authors.lastname: Birch
authors.forename: Matthew
authors.initials: M
authors.lastname: Laye
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.forename: Åse Bengaard
authors.initials: ÅB
authors.lastname: Andersen
authors.forename: Susanne Dam
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D006679:HIV Seropositivity; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000276:immunology; D016615:Telomere / Q000235:genetics; D019562:Viral Load
chemical_list: D020395:Receptors, Interleukin-7