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J. Virol. doi:10.1128/JVI.01809-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Frequency and phenotype of JC Virus-specific CD8⁺ T lymphocytes in the peripheral blood of patients with Progressive Multifocal Leukoencephalopathy

Department of Neurology and Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School. School of Medicine, Federal University of Rio de Janeiro, Center for Neurovirology and Cancer Biology, Temple University, Departments of Neurology and Medicine, Washington University School of Medicine, Division of Infectious Diseases and Department of Neurology, Massachusetts General Hospital, Harvard Medical School. Department of Neurology, University of Kentucky College of Medicine

^* To whom correspondence should be addressed. Email: ikoralni{at}bidmc.harvard.edu.

	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 (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 HIV⁺ individuals and nine HIV⁺ PML survivors. After magnetic pre-enrichment of CD8⁺ T cells, epitope-specific cells ranged from 0.001% to 0.22% by tetramer staining with no significant difference between the three study groups.

Using 7 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, 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.

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