Interfacial actin protrusions mechanically potentiate killing by cytotoxic T cells

摘要: Cytotoxic T lymphocytes (CTLs) kill by forming immunological synapses with target cells and secreting toxic proteases the pore protein perforin into intercellular space. Immunological are highly dynamic structures that potentiate activity applying mechanical force against cell. Here, we employed high-resolution imaging microfabrication to investigate how CTLs exert synaptic forces coordinate their output secretion. Using micropatterned stimulatory substrates enable synapse growth in three dimensions, found release occurs at base of actin-rich protrusions extend from central intermediate locations within synapse. These protrusions, which depended on cytoskeletal regulator WASP Arp2/3 actin nucleation complex, were required for exertion efficient killing. They also mediated physical distortion cell surface during CTL-target interactions. Our results reveal basis cellular cytotoxicity highlight functional importance dynamic, three-dimensional architecture immune cell-cell interfaces.