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 language | English |
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Pages (from-to) | 248-256 |
Number of pages | 9 |
Journal | Virology |
Volume | 269 |
Issue number | 2 |
DOIs | |
State | Published - 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