Abstract
The human polyomavirus JC (JCV) infects most healthy adults without causing any disease. In the setting of severe deficit of cell-mediated immunity, such as in acquired immunodeficiency syndrome (AIDS), malignancies or in organ transplant recipients, JCV can reactivate and cause progressive multifocal leukoencephalopathy (PML), a deadly demyelinating disease of the central nervous system. The humoral immune response, measured by the presence of virus-specific immunoglobulin G (IgG) in the blood or by intrathecal synthesis of IgG in the cerebrospinal fluid (CSF), is unable to contain the progression of PML. CD4+ T lymphocytes recognize extracellular viral proteins that have been degraded into peptides through the exogenous pathway and presented on major histocompatibility complex (MHC) class II molecules at the surface of antigen-presenting cells. Consistent with their underlying immunosuppression, the proliferative response of CD4+ T lymphocytes to mitogens or JCV antigens is reduced in PML patients. CD8+ cytotoxic T lymphocytes recognize intracellularly synthesized viral proteins that have been degraded into peptides through the endogenous pathway, and presented on MHC class I molecules at the surface of virus-infected cells. One of such JCV peptide, the VP1p100 ILMWEAVTL, has been characterized as a cytotoxic T lymphocyte (CTL) epitope in HLA-A* 0201+ PML survivors. Staining with the corresponding A*0201/JCV VP1p100 tetrameric complex showed that vp1P100-stimulated peripheral blood mononuclear cells (PBMCs) of 5/7 (71%) PML survivors had JCV-specific CTL, versus none of 6 PML progressors (P =.02). This cellular immune response may therefore be crucial in the prevention of PML disease progression and the tetramer staining assay may be used as a prognostic marker in the clinical management of these patients.
Original language | English (US) |
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Pages (from-to) | 59-65 |
Number of pages | 7 |
Journal | Journal of neurovirology |
Volume | 8 |
Issue number | SUPPL. 2 |
DOIs | |
State | Published - 2002 |
Keywords
- Acquired immunodeficiency syndrome (AIDS)
- Cytotoxic T lymphocyte (CTL)
- Human immunodeficiency virus (HIV)
- JC virus (JCV)
- Progressive multifocal leukoencephalopathy (PML)
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Virology