Intrathecal antibody production in an animal model of multiple sclerosis

Although the central nervous system (CNS) is thought to be immunoprivileged, under special circumstances it can produce antibody. Antibody production within the CNS, called intrathecal antibody production (ITAbP), is a prominent feature of neurological infections and inflammatory diseases, and is thought to possibly contribute to disease in multiple sclerosis (MS), but it has not been extensively studied. We investigated ITAbP in a viral model of MS. ELISpot, real-time RT-PCR for IgG mRNA in CNS tissue, and CSF analysis were used to assess ITAbP in two types of SJL mice infected with one of two strains of Theiler's murine encephalomyelitis virus (TMEV). The amplitude of ITAbP increased during the first 4 months of infection. TMEV viral load remained high during the course of the infection, which likely was the main stimulus for ITAbP, since within samples of infected CNS tissues, levels of IgG gene expression were highly correlated with viral RNA levels, and a large percentage of intrathecally produced antibody was directed against TMEV. This study provides the first extensive analysis of ITAbP in TMEV infection, and demonstrates that, in this animal model of MS, antibody production within the CNS is likely driven by the presence of the causative pathogen. (c) 2007 Elsevier B.V. All rights reserved.