CD8+ T Cells in the Central Nervous System of Mice With Herpes Simplex Infection are Highly Activated and Express High Levels of CCR5 and CXCR3

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold><jats:italic>Background:</jats:italic></jats:bold><jats:italic> </jats:italic>Herpes simplex virus type 2 (HSV-2) is a neurotropic virus that can cause meningitis, an inflammation of the meninges in the central nervous system. T cells are key players in viral clearance, and these cells migrate from peripheral blood into the central nervous system upon infection. Several factors contribute to T cell migration, including the expression of chemokines in the inflamed tissue that attract T cells through their expression of chemokine receptors. Here we investigated CD8+ T cell profile in the spinal cord in a mouse model of herpes simplex virus type 2neuroinflammation. <jats:bold><jats:italic>Method:</jats:italic></jats:bold><jats:italic> </jats:italic>Mice were infected with HSV-2, and sacrificed when showing signs of neuroinflammation. Cells and/or tissue from spinal cord, spleen and bloodwere analyzed for viability, expression of activation markers, chemokinereceptors and chemokines. Statistics were calculated using students T test and one-way ANOVA.<jats:bold><jats:italic>Results:</jats:italic></jats:bold>High numbers of CD8+ T cellswere present in thespinal cord following genital HSV-2-infection.CD8+T cells were highly activated and HSV-2 glycoprotein B -specific effector cells, some of which showed signs of recent degranulation. They also expressed high levels of many chemokine receptors, in particular CCR2, CCR4, CCR5 and CXCR3. Investigating corresponding receptor ligands in spinal cord tissue revealed markedly increased expression of the cognate ligands CCL2, CCL5, CCL8,CCL12 and CXCL10. <jats:bold><jats:italic>Conclusion:</jats:italic></jats:bold><jats:italic> </jats:italic>This study shows thatduring herpesvirus neuroinflammation anti-viralCD8+T cells accumulatein the CNS. CD8+ T cells in the CNS also express chemotactic receptors cognate to the chemotactic gradients in the spinal cord. This indicates that anti-viral CD8+ T cells may migrate to infected areas in the spinal cord during herpesvirus neuroinflammation in response to chemotactic gradients.</jats:p>