Detection of JC virus-specific cytotoxic T lymphocytes in healthy individuals.
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 VPp1100 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.
Division of Viral Pathogenesis and Department of Neurology, Research East, Room 213B, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. ikoralni@bidmc.harvard.edu
R A
RA
Du Pasquier
J E
JE
Schmitz
J
J
Jean-Jacques
Y
Y
Zheng
J
J
Gordon
K
K
Khalili
N L
NL
Letvin
I J
IJ
Koralnik
D000328:Adult; D003587:Cytomegalovirus / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007121:Immunocompetence; D016056:Immunodominant Epitopes; D007577:JC Virus / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D010940:Plant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D004268:DNA-Binding Proteins; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010940:Plant Proteins; D015534:Trans-Activators; D014157:Transcription Factors