Cytoskeleton dependent T cell polarization modulates calcium signals (35.31)

Abstract

Abstract The objective of the study was to analyze the role of T cell polarization and T cell shape changes for calcium (Ca) signals and Ca dependent T cell activation. We have used sophisticated live cell imaging technology to quantify cytoskeletal components, mitochondria and other organelle rearrangements during and after formation of the immunological synapse (IS) in parallel with Ca signals. We found that T cell polarization after formation of the IS was paralleled by drastic cell shape changes. These changes were dependent on the actin cytoskeleton and they induced a very intimate proximity between mitochondria and the plasma membrane at the IS. The mitochondrial translocation to the IS was Ca dependent but did not require local Ca influx at the IS. The shape change-dependent mitochondrial translocation to the plasma membrane prevented ORAI1 channel inactivation even in T cells in which dynein motor protein-dependent mitochondria movements towards the plasma membrane were completely abolished, highlighting the importance of the cell shape to control Ca influx. Our results suggest that cell shape changes do not only facilitate an efficient contact with antigen presenting cells but also strongly modulate Ca dependent T cell activation. Organelle polarization during IS formation is an important mechanism to modulate Ca dependent T cell activation. This project was funded by the Deutsche Forschungsgemeinschaft (Graduate Research School 1326, SFB 530, project A3) and a HOMFOR grant from the Medical Faculty.