title: Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy.
abstract: JC virus (JCV)-specific CD8+ cytotoxic T lymphocytes (CTL) are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine the frequency and phenotype in fresh blood of CD8+ T cells specific for two A*0201-restricted JCV epitopes, VP1(p36) and VP1(p100), and assess their impact on JC and BK viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with PML (HIV+ PML patients) classified as survivors. After magnetic pre-enrichment of CD8+ T cells, epitope-specific cells ranged from 0.001% to 0.022% [corrected] by tetramer staining, with no significant difference among the three study groups. By use of seven-color flow cytometry, there was no predominant differentiation phenotype subset among JCV-specific CD8+ T cells in healthy individuals, HIV+ subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the acute phase, there was a majority of activated effector memory cells. BKV DNA was undetectable in all blood samples by quantitative PCR, while a low JC viral load was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV DNA were detected in 33.3% and 13.3% of all urine samples, respectively, independent of the presence of JCV-specific CTL. The detection of JCV DNA in the urine was associated with the presence of a JCV VP1(p100) CTL response. Immunotherapies aiming at increasing the cellular immune response against JCV may be valuable in the treatment of HIV+ individuals with PML.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Lima
authors.forename: Angela
authors.initials: A
authors.lastname: Marzocchetti
authors.forename: Patrick
authors.initials: P
authors.lastname: Autissier
authors.forename: Troy
authors.initials: T
authors.lastname: Tompkins
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gordon
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Rajesh T
authors.initials: RT
authors.lastname: Gandhi
authors.forename: Nagagopal
authors.initials: N
authors.lastname: Venna
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Berger
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000328:Adult; D000368:Aged; D001739:BK Virus / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007577:JC Virus / Q000145:classification / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007958:Leukocyte Count; D007968:Leukoencephalopathy, Progressive Multifocal / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008875:Middle Aged; D010641:Phenotype; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D013997:Time Factors; D015678:Viral Structural Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D015678:Viral Structural Proteins; D017493:Leukocyte Common Antigens