Formation of in vivo immunological synapses (IS) between CTLs and virally infected astrocytes leads astrocyte to polarization mediated by the activation of a Rho‐GTPase signaling pathway.

Immunological synapses (IS) mediate intercellular communication between T cells and APCs. T cell polarization at the Kupfer‐type IS consists of a peripheral supramolecular activation cluster (pSMAC), which is high in LFA‐1, and a central SMAC, high in TCR. Target virally infected astrocytes also polarize towards the immunological synapse in vivo . Astrocyte polarization in response to physical lesions in vitro is mediated through the activation of a signaling pathway mediated by a family of Rho‐GTPases, and coordinated by Cdc42. Here we tested the hypothesis that that stimulation of a Rho‐GTPase cascade underlies astrocyte polarization in response to an immune attack in vitro and in vivo . To do so, we infected brain astrocytes with a novel adenoviral (Ad) vector expressing a dominant negative variant of Cdc42 (Cdc42DN) and Thymidine Kinase (TK), a marker of infected cells, and analyzed their responses to a T cell attack. We show that during an anti‐viral immune response, infected astrocytes contacted by CTLs become polarized through the activation of a Rho‐GTPase signaling pathway. This work was funded by grants from NINDS/NIH.