Protection of CD3 δ knockout mice from lymphocytic choriomeningitis virus-induced immunopathology: Implications for viral neuroinvasion

Dietmar J. Kappes, Diane M.P. Lawrence, Melinda M. Vaughn, Vibhuti P. Davé, Alec R. Belman, Glenn F. Rall

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

For a virus to establish a neuronal infection, it must spread from its primary site of infection to the central nervous system (CNS) before immune- mediated clearance occurs. Lymphocytic choriomeningitis virus (LCMV) is a murine pathogen that can result in persistent neuronal infection in newborn mice and in adults that lack CD8+ T cells. To determine the neuroinvasive capacity of LCMV in the presence of an existent, but compromised, cytotoxic T lymphocyte response, the course of LCMV infection was examined in mice that possess 10% of the normal complement of T lymphocytes, due to the lack of the CD3 δ (δ) subunit of the T cell receptor complex (CD3 δ KO mice). Unlike immunocompetent mice that produced a massive immune response that caused death by 6-7 days postinfection, CD3 δ KO mice mounted a weak response and survived. The presence of viral antigen gradually shifted from the class I MHC-positive meninges and ependyma to class I MHC-deficient CNS neurons 10-30 days postinoculation. The infected CD3 δ KO mice developed a delayed T cell response that suppressed virus replication in peripheral tissues but not in the CNS; subsequent adoptive transfer experiments supported the hypothesis that the lack of clearance from neurons was due to sequestration of LCMV in an immune-privileged cell type. Based on these results, we propose that a critical parameter in the pathogenesis of neurotropic viruses is the rate of immune activation; individuals with impaired T cell responses may be more vulnerable to persisting CNS infections. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalVirology
Volume269
Issue number2
DOIs
StatePublished - Apr 10 2000

Keywords

  • Adoptive Transfer
  • Animals
  • Brain/immunology
  • CD3 Complex/physiology
  • CD8-Positive T-Lymphocytes/immunology
  • Cell Line
  • Chlorocebus aethiops
  • Cricetinae
  • Lymphocytic Choriomeningitis/immunology
  • Lymphocytic choriomeningitis virus/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • T-Lymphocytes, Cytotoxic/immunology
  • Vero Cells

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