CD8+ T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1β and cathepsin D

We recently reported that human dendritic cells release the leaderless secretory protein interleukin-1beta (IL-1beta) following specific interaction with alloreactive T lymphocytes. To clarify the molecular mechanism underlying this secretion, this study investigated the intracellular trafficking of IL-1beta in dendritic cells and the signal(s) regulating its release. Results show that a fraction of the intracellular IL-1beta precursor colocalizes with the hydrolase cathepsin D in endolysosomes of dendritic cells; secretion of both proteins is elicited by stimuli that induce intracellular calcium increases. Alloreactive CD8(+) T lymphocytes generate a Ca(++) influx in dendritic cells followed by enrichment in endolysosomes containing IL-1beta and cathepsin D beneath the membrane in contact with T cells. These events result in polarized exocytosis of secretory lysosomes, mediated by microtubules, with release of IL-1beta and cathepsin D toward the interacting CD8(+) T cell.