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.
Du Pasquier
R A
RA
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
Schmitz
J E
JE
Jean-Jacques
J
J
Zheng
Y
Y
Gordon
J
J
Khalili
K
K
Letvin
N L
NL
Koralnik
I J
IJ
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