Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System

Christian Wüthrich, Stephanie Batson, Igor J. Koralnik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 control subjects. Neurons predominantly sustained a restrictive infection with expression of JCV regulatory protein T antigen (T Ag), whereas glial cells were productively infected and expressed both T Ag and the capsid protein VP1. T cells were more prevalent near JCV-infected cells with intact nuclei expressing both T Ag and VP1 compared with those expressing either protein alone. CD8-positive T cells also colocalized more with JCV-infected glial cells than with JCV-infected neurons. Major histocompatibility complex class I expression was upregulated in JCV-infected areas but could only be detected in rare neurons interspersed with infected glial cells. These results suggest that isolated neurons harboring restrictive JCV infection do not upregulate major histocompatibility complex class I and thus may escape recognition by CD8-positive T cells.

Original languageEnglish (US)
Pages (from-to)791-803
Number of pages13
JournalJournal of neuropathology and experimental neurology
Volume74
Issue number8
DOIs
StatePublished - Aug 31 2015

Keywords

  • CD8-positive T cells
  • Immune response
  • JC virus
  • JCV encephalopathy
  • JCV granule cell neuronopathy
  • Major histocompatibility complex class I
  • Neurons
  • Progressive multifocal leukoencephalopathy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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