Theiler's murine encephalomyelitis virus infection of astrocytes induces the expression of chemokines which attract activated but not resting T lymphocytes

In this article, we studied the production of the chemokine CXCL9, also termed Mig (monokine induced by gamma interferon) by cultured SJL/J mouse astrocytes infected with the BeAn strain of Theiler’s murine encephalomyelitis virus (TMEV). This picornavirus induces demyelination in the SJL/J genetically susceptible strain of mice through an immune process mediated by CD4+ Th1 T cells. Those cells were chemoattracted by chemokines inside the central nervous system (CNS) after blood-brain barrier (BBB) disruption. cRNAs from TMEV- and mock-infected astrocytes cells were hybridized to the Affymetrix murine genome U74v2 DNA microarray. Hybridization data analysis revealed the upregulation of six sequences potentially coding for Mig. We confirmed post infection Mig mRNA increase by quantitative (qPCR) and RT-PCR. The presence of Mig in the supernatants of infected astrocytes was quantified using a specific ELISA. Secreted Mig was biologically active, inducing chemoattraction of mouse activated CD4+ T lymphocytes. Conversely, attracting activity on CD3+ resting T cells that can be attributed to chemokines as CXCL12/SDF-1α could not be demonstrated in these supernatants. No overinduction of the gene coding for this chemokine was assessed by DNA hybridization either. Both recombinant IFN-γ and TNF-α inflammatory cytokines were also strong inducers of Mig in SJL/J astrocyte cultures.