JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression. The nature of the immune response that contains replication of this virus is unknown. We have explored JCV-specific cellular immune responses in patients with PML and control subjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) of four human immunodeficiency virus (HIV)-infected patients who were survivors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulatory protein or the VP1 major capsid protein. This lysis was mediated by CD8(+) T lymphocytes and was major histocompatibility complex class I restricted. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who had progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients.
Koralnik
I J
IJ
Department of Neurology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ikoralni@caregroup.harvard.edu
Du Pasquier
R A
RA
Letvin
N L
NL
D000952:Antigens, Polyomavirus Transforming / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D036022:Capsid Proteins; D015395:Histocompatibility Antigens Class I; C062481:VP1 protein, polyomavirus