Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathy

Igor J. Koralnik*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

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 languageEnglish (US)
Pages (from-to)59-65
Number of pages7
JournalJournal of neurovirology
Volume8
Issue numberSUPPL. 2
DOIs
StatePublished - 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

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