title: Immunoregulatory T cells may be involved in preserving CD4 T cell counts in HIV-infected long-term nonprogressors and controllers.
abstract: BACKGROUND
  HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell counts in controllers and in LTNPs.
  
  
  METHODS
  Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17 cells, and CD3+CD8+CD161(high)Tc17 cells in peripheral blood were measured using flow cytometry. Tregs in lymphoid tissue were determined in tonsil biopsies and evaluated using immunolabeling. The production of transforming growth factor beta (TGF-β), interleukin (IL)-10, and IL-17 upon stimulation with phytohemagglutinin in peripheral blood was determined by Luminex.
  
  
  RESULTS
  All groups of HIV-infected patients displayed similar percentages of Tregs in both peripheral blood and lymphoid tissue. However, a larger percentage of Tregs in ECs and LTNPs were activated compared with that in controls, progressors, and viremic controllers. Further, ECs as the only group of HIV-infected patients, displayed elevated percentages of CD161+Th17 cells, preserved CD3+CD8+CD161(high)Tc17 cells, and preserved IL-10 production.
  
  
  CONCLUSIONS
  Overall, Treg percentage was similar in both blood and lymphoid tissue in all groups of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors.
authors.affiliation: *Viro-Immunology Research Group, Departments of Infectious Diseases; †Clinical Immunology; ‡Pathology; and §Oto-Rhinolaryngology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark; ‖Department of Infectious Diseases, Hvidovre Hospital, University Hospital of Copenhagen, Copenhagen, Denmark; and ¶Department of Infectious Diseases, Odense Hospital, University of Southern Denmark, Odense, Denmark.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Gaardbo
authors.forename: Andreas
authors.initials: A
authors.lastname: Ronit
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Hartling
authors.forename: Lise M R
authors.initials: LM
authors.lastname: Gjerdrum
authors.forename: Karoline
authors.initials: K
authors.lastname: Springborg
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiær
authors.forename: Kristina
authors.initials: K
authors.lastname: Thorsteinsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.forename: Åse B
authors.initials: ÅB
authors.lastname: Andersen
authors.forename: Susanne D
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D020276:HIV Long-Term Survivors; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D016131:Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology*; D058504:Th17 Cells / Q000276:immunology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D017252:CD3 Complex; D020381:Interleukin-17; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016212:Transforming Growth Factor beta; D016753:Interleukin-10