Previous Article | Next Article 
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,
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.
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.
This article has been cited by other articles:
-
Nived, O, Bengtsson, A., Jonsen, A, Sturfelt, G
(2008). Progressive multifocal leukoencephalopathy - the importance of early diagnosis illustrated in four cases. Lupus
17: 1036-1041
[Abstract]
-
Yang, W, Beaudoin, E., Lu, L, Du Pasquier, R., Kuroda, M., Willemsen, R., Koralnik, I., Junghans, R.
(2007). Chimeric immune receptors (CIRs) specific to JC virus for immunotherapy in progressive multifocal leukoencephalopathy (PML). Int Immunol
19: 1083-1093
[Abstract]
[Full Text]
-
Lima, M. A., Marzocchetti, A., Autissier, P., Tompkins, T., Chen, Y., Gordon, J., Clifford, D. B., Gandhi, R. T., Venna, N., Berger, J. R., Koralnik, I. J.
(2007). Frequency and Phenotype of JC Virus-Specific CD8+ T Lymphocytes in the Peripheral Blood of Patients with Progressive Multifocal Leukoencephalopathy. J. Virol.
81: 3361-3368
[Abstract]
[Full Text]
-
Khalili, K., White, M. K., Lublin, F., Ferrante, P., Berger, J. R.
(2007). Reactivation of JC virus and development of PML in patients with multiple sclerosis. Neurology
68: 985-990
[Abstract]
[Full Text]
-
Li, J., Melenhorst, J., Hensel, N., Rezvani, K., Sconocchia, G., Kilical, Y., Hou, J., Curfman, B., Major, E., Barrett, A. J.
(2006). T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus.. J. Gen. Virol.
87: 2951-2960
[Abstract]
[Full Text]
-
Chen, Y., Trofe, J., Gordon, J., Du Pasquier, R. A., Roy-Chaudhury, P., Kuroda, M. J., Woodle, E. S., Khalili, K., Koralnik, I. J.
(2006). Interplay of Cellular and Humoral Immune Responses against BK Virus in Kidney Transplant Recipients with Polyomavirus Nephropathy.. J. Virol.
80: 3495-3505
[Abstract]
[Full Text]
-
Podolsky, D. K.
(2005). Selective adhesion-molecule therapy and inflammatory bowel disease -- a tale of janus?. NEJM
353: 1965-1968
[Full Text]
-
Krymskaya, L., Sharma, M. C., Martinez, J., Haq, W., Huang, E. C., Limaye, A. P., Diamond, D. J., Lacey, S. F.
(2005). Cross-Reactivity of T Lymphocytes Recognizing a Human Cytotoxic T-Lymphocyte Epitope within BK and JC Virus VP1 Polypeptides. J. Virol.
79: 11170-11178
[Abstract]
[Full Text]
-
Berger, J. R., Koralnik, I. J.
(2005). Progressive Multifocal Leukoencephalopathy and Natalizumab -- Unforeseen Consequences. NEJM
353: 414-416
[Full Text]