Human T cell activation induces synaptic translocation and alters expression of the serine protease inhibitor neuroserpin and its target protease

ABSTRACT Contact between T cells and APCs and activation of aneffective immune response trig ger cellular polarization andthe formation of a structured interface known as theimmunological synapse. Interactions across the synapseand secretion of T cell and APC-derived factors into theperisynaptic compartment regulate synapse formation andactivation of T cells. We report that the serine proteaseinhibitor neuroserpin, an axonally secreted protein thoughtto play roles in the formation of the neuronal synapse andrefinement of synaptic activity, is expressed in human na ¨iveeffector memory and central memory subsets of CD4 + andCD8 + T cells, as well as monocytes, B cells, and NK cells.Neuroserpin partially colocalized with a TGN38/LFA-1-positive vesicle population in T cells and translocates to theimmunological synapse upon activation with TCR anti-bodies or antigen-pulsed APCs. Activation of T cells trig-gered neuroserpin secretion, a rapid, 8.4-fold up-regulation of the serine protease tissue plasminogenactivator, the protease target for neuroserpin, anda delayed, 6.25-fold down-regulation of neuroserpin ex-pression. Evidence of polarization and regulated neuro-serpin expression was also seen in ex vivo analyses ofhuman lymph nodes and blood-derived T cells. Increasedneuroserpin expression was seen in clusters of T cells inthe paracortex of human lymph nodes, with some showingpolarization to areas of cell:cell interaction. Our resultssupport a role for neuroserpin and tissue plasminogenactivator in activation-controlled proteolytic cleavage ofproteins in the synaptic or perisynaptic space to modulateimmune cell function. J. Leukoc. Biol. 97: 000–000; 2015.