Early T cell response in the central nervous system in canine distemper virus infection

A. Tipold, Peter F Moore, A. Zurbriggen, I. Burgener, G. Barben, M. Vandevelde

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The initial demyelinating lesions in canine distemper virus (CDV) infection develop during a period of severe immunosuppression in the absence of inflammation. In vitro and in vivo studies suggest that early demyelination is due to directly virus-induced oligodendroglial changes. In the present spatiotemporal study in experimentally CDV-infected dogs we observed diffuse up-regulation of T cells throughout the central nervous system (CNS) and T cell invasion in early demyelinating lesions. Invasion of T cells in the CNS occurred despite severe immunosuppression and without any perivascular cuffing. However, the major fraction of invading T cells correlated with sites of viral replication and coincided with the demonstration of an early immune response against the nucleocapsid protein of CDV. Activation of microglial cells was thought to have elicited the migration of T cells to the CNS by secretion of chemokines: marked IL-8 activity was found in the CSF of dogs with acute lesions. In areas of early demyelination, large numbers of CD3+ cells accumulated in the tissue in the absence of any morphological sign of inflammation. Whether the T cells at lesion sites contribute to the development of acute demyelination remains uncertain at this stage. Antiviral cytotoxicity was not apparent since viral clearance in demyelinating lesions is only effective when B cells and concurring antiviral antibody production appeared in the subacute and chronic inflammatory stage of the disease. CD3+ cells appear to persist for several weeks after infection since they were also found in recovered dogs that did not develop demyelination. Accumulation of immune cells, including a significant proportion of resting T cells (CD45RA+) in the CNS in the early stages of the disease may facilitate the later development of the intrathecal immune response and associated immunopathological complications.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalActa Neuropathologica
Volume97
Issue number1
DOIs
StatePublished - Jan 1999

Keywords

  • Acute demyelination
  • Canine distemper virus
  • Immunosuppression
  • T cells

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

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