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Journal of Virology, September 2004, p. 10206-10210, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10206-10210.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Detection of JC Virus-Specific Cytotoxic T Lymphocytes in Healthy Individuals

R. A. Du Pasquier,1,2,{dagger} J. E. Schmitz,1 J. Jean-Jacques,1 Y. Zheng,1 J. Gordon,3 K. Khalili,3 N. L. Letvin,1 and I. J. Koralnik1,2*

Division of Viral Pathogenesis,1 Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,2 Center for Neurovirology and Cancer Biology, Temple University, Philadelphia, Pennsylvania3

Received 28 January 2004/ Accepted 4 May 2004

The polyomavirus JC (JCV) infects 85% of healthy individuals, and its reactivation in a limited number of immunosuppressed people causes progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. We hypothesized that JCV-specific cytotoxic T lymphocytes (CTLs) might control JCV replication in healthy individuals, blocking the evolution of PML. Using 51Cr release and tetramer staining assays, we show that 8 of 11 HLA-A*0201+ healthy subjects (73%) harbor detectable JCV-specific CD8+ CTLs that recognize one or two epitopes of JCV VP1 protein, the HLA-A*0201-restricted VP1p36 and VP1p100 epitopes. We determined that the frequency of JCV VP1 epitope-specific CTLs varied from less than 1/100,000 to 1/2,494 peripheral blood mononuclear cells. More individuals had JCV VP1-specific than cytomegalovirus-specific CTLs (8 of 11 subjects [73%] versus 2 of 10 subjects [20%], respectively). These results show that a CD8+-T-cell response against JCV is commonly found in immunocompetent people and suggest that these cells might protect against the development of PML.

* Corresponding author. Mailing address: Division of Viral Pathogenesis and Department of Neurology, Research East, Room 213B, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Phone: (617) 667-1568. Fax: (617) 667-8210. E-mail: ikoralni{at}bidmc.harvard.edu.

{dagger} Present address: Division of Neurology and Division of Immunology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Journal of Virology, September 2004, p. 10206-10210, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10206-10210.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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