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

Abstract

ABSTRACT 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 51 Cr 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 VP1 p36 and VP1 p100 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.