title: CD4 T cell expansions are associated with increased apoptosis rates of T lymphocytes during IL-2 cycles in HIV infected patients.
abstract: OBJECTIVE
  In an attempt to determine the mechanisms underlying the CD4 T cell expansions in patients receiving intermittent interleukin (IL)-2, a cohort of 10 HIV infected patients were studied during a 5-day cycle of IL-2 to measure rates of apoptosis, the expression of activation markers in CD4 and CD8 T cell subsets and the serum levels of proinflammatory cytokines. All patients were receiving highly active antiretroviral therapy.
  
  
  METHODS
  Peripheral blood mononuclear cells were tested pre- and at the completion of IL-2 treatment with annexin V/7-AAD for the measurement of apoptosis. Phenotypic analyses of T lymphocytes were performed in parallel. Serum levels of interferon (IFN)gamma, granulocyte-macrophage colony stimulating factor, IL-6 and tumor necrosis factor (TNF)alpha were tested by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  IL-2 increased the spontaneous apoptosis rates of CD4 and CD8 T lymphocytes (P = 0.003). Expression of HLA-DR, CD38 and CD95 increased on both CD4 and CD8 T lymphocytes whereas CD25 induction was observed exclusively on CD4 T cells. Significant increases of serum IL-6 and TNFalpha levels were noted in all patients whereas viral loads remained unchanged.
  
  
  CONCLUSIONS
  Administration of IL-2 for 5 days in HIV infected patients leads to enhanced apoptosis of both CD4 and CD8 T cells despite an eventual increase of the CD4 T cell count. A profound activation state with induction of activation markers on T cells and high levels of TNFalpha and IL-6 accompanies the increased apoptosis during the IL-2 cycle. These data suggest that the CD4 expansions seen in the context of intermittent IL-2 therapy are the net result of increases in both cell proliferation and cell death.
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD 20892, USA.
authors.forename: I
authors.initials: I
authors.lastname: Sereti
authors.forename: B
authors.initials: B
authors.lastname: Herpin
authors.forename: J A
authors.initials: JA
authors.lastname: Metcalf
authors.forename: R
authors.initials: R
authors.lastname: Stevens
authors.forename: M W
authors.initials: MW
authors.lastname: Baseler
authors.forename: C W
authors.initials: CW
authors.lastname: Hallahan
authors.forename: J A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: R T
authors.initials: RT
authors.lastname: Davey
authors.forename: H C
authors.initials: HC
authors.lastname: Lane
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000008:administration & dosage*; D008213:Lymphocyte Activation; D008297:Male; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D019562:Viral Load
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D015375:Receptors, Interleukin-2