title: Critical role of JC virus-specific CD4 T-cell responses in preventing progressive multifocal leukoencephalopathy.
abstract: BACKGROUND
  JC virus (JCV) is ubiquitous among the general population. However, only individuals with severely impaired immunity, mainly AIDS patients, develop progressive multifocal leukoencephalopathy (PML). Here, we examined the role of specific CD4 T cells in the control of JCV infection.
  
  
  METHODS
  JCV-specific CD4 T-cell responses were investigated by assaying peripheral blood mononuclear cell proliferation in response to the purified virus. Four groups of individuals without PML were examined: 14 HIV-seronegative healthy donors and 25 HIV-infected patients without PML, separated into urinary JCV excretors (active infection) and non-excretors, according to JCV PCR on urine. Two groups of patients with PML were also studied: 14 HIV-infected patients with active PML; and 10 PML survivors on effective and prolonged antiretroviral therapy. All of the patients were PCR-positive for JCV in the cerebrospinal fluid at the time of diagnosis of PML.
  
  
  RESULTS
  No significant anti-JCV CD4 T-cell proliferation was found in any of the non-excretors tested. All nine healthy donors and seven of the 13 non-PML HIV-infected patients with urinary JCV excretion had positive JCV-specific CD4 T-cell responses. No significant response was found in the 14 patients with active PML, while nine of the 10 PML survivors had positive responses. Restoration of JCV-specific CD4 T-cell responses was associated with JCV clearance from the cerebrospinal fluid.
  
  
  CONCLUSIONS
  JCV-specific CD4 T-cell responses appear to play a critical role in the control of JCV infection, preventing PML development. Such responses can be restored in PML survivors following effective and prolonged antiretroviral therapy.
authors.affiliation: INSERM E-0109, AP-HP, CHU de Bicêtre, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Gasnault
authors.forename: Mufide
authors.initials: M
authors.lastname: Kahraman
authors.forename: Marie Ghislaine
authors.initials: MG
authors.lastname: de Goër de Herve
authors.forename: Deniz
authors.initials: D
authors.lastname: Durali
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Yassine
authors.initials: Y
authors.lastname: Taoufik
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D005814:Genes, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007577:JC Virus / Q000235:genetics; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology* / Q000821:virology; D016133:Polymerase Chain Reaction / Q000379:methods; D017201:Virus Shedding