title: HIV controllers are distinguished by chemokine expression profile and HIV-specific T-cell proliferative potential.
abstract: BACKGROUND
  HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers.
  
  
  METHODS
  Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses.
  
  
  RESULTS
  HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control.
  
  
  CONCLUSIONS
  Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Card
authors.forename: Yoav
authors.initials: Y
authors.lastname: Keynan
authors.forename: Julie
authors.initials: J
authors.lastname: Lajoie
authors.forename: Courtney P
authors.initials: CP
authors.lastname: Bell
authors.forename: Magdy
authors.initials: M
authors.lastname: Dawood
authors.forename: Marissa
authors.initials: M
authors.lastname: Becker
authors.forename: Ken
authors.initials: K
authors.lastname: Kasper
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014779:Virus Replication / Q000276:immunology
chemical_list: D016207:Cytokines