Electronic Poster | Session 2

003 – Proinflammatory T cells drive distinct inflammatory astrocyte profiles

Samantha Schmaul (1) – Nicholas Hanuscheck (1) – Frauke Zipp (1) – Stefan Bittner (1)
Johannes Gutenberg University Mainz, University medical center Mainz, Mainz, Germany (1)

Highly proinflammatory CD4+ Th1 and Th17 T cells are able to infiltrate CNS tissue and to initiate an inflammatory cascade involving innate immune activation, oligodendrocyte and neuronal damage. The role of astrocytes during autoimmune CNS inflammatory diseases such as multiple sclerosis, however, is still poorly understood. It is especially unclear how they interact with invading immune cells and what drives astrocytes to overtake proinflammatory or neuroprotective roles in tissue inflammation.
During tissue invasion, Th1 and Th17 cells require antigenic restimulation to exert their encephalitogenic potential. Because astrocytes do not express MHC class II under physiological conditions, T cell stimulation in the CNS is yet considered to be mainly provided by local myeloid cells. Here, using two-photon live imaging, we show that pathogenic T cells directly interact with astrocytes in Aldh1l1-eGFP reporter organotypic hippocampal slice cultures (OHSCs). We demonstrate that T cell infiltration induces MHC class II expression on astrocytes, indicating an antigen dependent interaction of T cells with astrocytes. Indeed, interacting CNS-autoantigen-specific T cells (2d2) showed prolonged interactions with astrocytes as compared to ovalbumin-specific T cells (OT2). Antibody-mediated blocking of MHC class II significantly increased T cell motility of MOG-specific T cells indicative of the acquisition of undirected search behaviour, while it did not alter OT2 T cell motility. Strikingly, we could identify distinct differences between Th1 and Th17 cells as astrocytes gained different adhesion molecule signatures upon their presence. In summary, we show that proinflammatory T lymphocytes initiate an inflammatory phenotype in astrocytes as a potential new modulator of neuroinflammatory pathways.