Presence of JC virus-specific CTL in the cerebrospinal fluid of PML patients: rationale for immune-based therapeutic strategies.

Details

Serval ID
serval:BIB_2FC2634CA270
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Presence of JC virus-specific CTL in the cerebrospinal fluid of PML patients: rationale for immune-based therapeutic strategies.
Journal
Aids
Author(s)
Du Pasquier R.A., Autissier P., Zheng Y., Jean-Jacques J., Koralnik I.J.
ISSN
0269-9370[print], 0269-9370[linking]
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
19
Number
18
Pages
2069-2076
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
OBJECTIVES: There is urgent need of a treatment for progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). To evaluate the rationale for immunotherapy of PML, we explored whether JCV-specific cytotoxic T lymphocytes (CTL) can penetrate the central nervous system (CNS). In addition, we studied the breadth of their T-cell receptor (TCR) repertoire, and sought to establish a reliable method to expand these cells in vitro. DESIGN AND METHODS: We enrolled 18 patients in this study, including 16 with proven or possible PML (15 HIV-positive and one HIV-negative), and two HIV-positive patients with other neurological diseases. Detection of JCV-specific CTL in the blood and the cerebrospinal fluid was performed by Cr release and tetramer staining assays in 15 patients. RESULTS: Of 11 PML patients with analyzable cerebrospinal fluid (CSF), two had no detectable JCV-specific CTL in the blood and CSF and died 3.7 and 7.2 months later. The nine remaining patients had an inactive course of PML and detectable JCV-specific CTL in the blood. In addition, four of them (44%) also had detectable JCV-specific CTL in the CSF. Both HIV-positive patients with OND had detectable JCV-specific CTL in the blood and one in the CSF. Using tetramer technology, we obtained highly enriched JCV-specific CTL lines that were able to kill target cells presenting JCV peptides. The breadth of the TCR repertoire was CTL epitope dependent. CONCLUSIONS: These results indicate that JCV-specific CTL are present in the CNS of PML patients and pave the way for an immune-based therapeutic approach.
Keywords
Adult, Capsid Proteins/cerebrospinal fluid, Cell Separation, Epitopes, T-Lymphocyte/cerebrospinal fluid, Female, Humans, Immunity, Cellular, Immunotherapy, JC Virus/isolation &amp, purification, Leukoencephalopathy, Progressive Multifocal/cerebrospinal fluid, Leukoencephalopathy, Progressive Multifocal/immunology, Male, Middle Aged, Receptors, Antigen, T-Cell, alpha-beta/analysis, T-Lymphocytes, Cytotoxic/virology
Pubmed
Web of science
Create date
25/01/2008 14:56
Last modification date
20/08/2019 13:14
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