Nuclear polarization to the immune synapse facilitates an early transcriptional burst.

Target cell recognition by cytotoxic T lymphocytes (CTLs) triggers rapid delivery of cytolytic granules to the immune synapse directed by the centrosome. Recent studies have also identified a rapid burst of T cell receptor (TCR)-activated transcription that contributes to CTL-mediated killing. To determine how de novo transcription might be coordinated with intracellular polarization, we asked when transcription factor translocation to the nucleus occurs relative to TCR activation and centrosome polarization within individual CTLs. Upon target cell recognition, the nucleus polarized to and contacted the immune synapse, preceding centrosome docking. The nucleus distorted as it moved, with transcription factors NFAT and NF-κB accumulating in the nucleus during polarization. Inhibition or deletion of myosin IIA prevented both nuclear polarization and transcription factor translocation. Thus, nuclear polarization facilitates an early transcriptional burst that occurs as CTLs encounter targets and the consequent delivery of newly synthesized cytokines to the immune synapse.