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Frequency and Phenotype of JC Virus-Specific CD8⁺ T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy

Department of Neurology,¹ Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,² School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil,³ Center for Neurovirology and Cancer Biology, Temple University, Philadelphia, Pennsylvania,⁴ Departments of Neurology and Medicine, Washington University School of Medicine, St. Louis, Missouri,⁵ Division of Infectious Diseases,⁶ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,⁷ Department of Neurology, University of Kentucky College of Medicine, Lexington, Kentucky⁸

Received 18 August 2006/ Accepted 3 January 2007

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 preenrichment of CD8⁺ T cells, epitope-specific cells ranged from 0.001% to 0.22% 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.

Published ahead of print on 17 January 2007.