title: Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.
abstract: BACKGROUND
  Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.
  
  
  METHODS
  To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.
  
  
  RESULTS
  The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006). These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy). As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001).
  
  
  CONCLUSIONS
  Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.
authors.affiliation: Division of Infectious Diseases, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, Ohio, United States of America.
authors.forename: Maura
authors.initials: M
authors.lastname: Manion
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.forename: Kathleen
authors.initials: K
authors.lastname: Medvik
authors.forename: Gareth
authors.initials: G
authors.lastname: Hardy
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Richard
authors.initials: R
authors.lastname: Pollard
authors.forename: David
authors.initials: D
authors.lastname: Asmuth
authors.forename: Robert
authors.initials: R
authors.lastname: Murphy
authors.forename: Edward
authors.initials: E
authors.lastname: Barker
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: Brady
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.forename: Nick
authors.initials: N
authors.lastname: Funderburg
authors.forename: Scott F
authors.initials: SF
authors.lastname: Sieg
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha