Target APC polarization at immunological synapses (IS) in vivo: infected astrocytes polarize towards CTL cells during the brain antiviral immune response. (91.13)

Abstract

Abstract IS mediate intercellular communication between T cells and APCs. T cells’ structure and membrane proteins are polarized at IS. T cell polarization at the IS consists of a peripheral supramolecular activation cluster (pSMAC), which is high in LFA-1, and low in TCR, and a central SMAC, high in TCR, and low in LFA-1. The MTOC, Golgi and secretory vesicles are also polarized towards the IS. Here we demonstrate that during an anti-viral immune response in the brain, APCs are also polarized. Brain astrocytes were infected with an adenoviral (Ad) vector expressing Thymidine Kinase (TK), a marker of infected cells. 30 days later we immunized systemically against Ads, and 14 days later animals were sacrificed and brains prepared for microscopical analysis. Brain sections were immunostained for TCR, LFA-1, TK, EAAT2, γ-Tubulin, α-Tubulin and GM130. Confocal analysis revealed that target infected astrocytes, normally a non-polarized cell, became completely repolarized. Target astrocytes retract all processes and form a single large protrusion towards the T cell. The MTOC and Golgi are then targeted towards and into the protrusion, and membrane proteins become polarized. These results demonstrate that CTL signaling, potentially mediated through IS, induces profound morphological changes in target APCs. This work was funded by grants from NINDS/NIH.